What does the research show about bismuth subsalicylate?

Bismuth subsalicylate

Older trials found daily bismuth subsalicylate lowered travelers' diarrhea, though a small 2025 trial found no difference, and it raised relief of infectious diarrhea against placebo. Added to H. pylori antibiotic regimens, bismuth raised eradication. Black stool and tongue are common. It contains salicylate, and its label warns about Reye's syndrome, aspirin allergy and blood thinners.

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Status: Bismuth subsalicylate is sold over the counter in the US (Pepto-Bismol, Kaopectate) to relieve travelers' diarrhea, diarrhea, and upset stomach from overindulgence, including heartburn, indigestion and nausea, for adults and children 12 and over. Another bismuth salt, bismuth subcitrate potassium, is prescription-only as part of Pylera, with metronidazole and tetracycline, FDA-approved with omeprazole to eradicate H. pylori in people with duodenal ulcer disease. Pylera carries a boxed warning on metronidazole and cancer in animals. Preventing travelers' diarrhea is not a labeled use.
Also called: Pepto-Bismol, Kaopectate, bismuth subsalicylate, BSS, pink bismuth, bismuth, bismuth subcitrate potassium, Pylera, bismuth quadruple therapy
Taken for: diarrhea, traveler's diarrhea, preventing traveler's diarrhea, upset stomach, heartburn, indigestion, nausea, H. pylori, stomach ulcers, diarrhea in children

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help4

ModerateShown to lower travelers' diarrhea in older trials, 14% on 2.1 g a day against 40% on placebo in Mexico. A small 2025 trial found no difference.
ModerateShown to raise relief of infectious diarrhea against placebo, odds ratio 3.7, though loperamide cut unformed stools more in a head-to-head trial.
ModerateShown to raise H. pylori eradication when bismuth was added to antibiotic regimens, odds ratio 1.83 overall and 2.81 as a simple add-on.
LimitedLimited evidence: two trials in hospitalized infants found shorter diarrhea on bismuth subsalicylate with rehydration, ending within 5 days in 88% to 89% against 74% on placebo.

Reported risks8

ModerateShown to darken stool, 15.6% on a bismuth regimen against 4.6% on a regimen without bismuth, and to darken the tongue. Labels describe it as temporary.Very common
ModerateShown in a network analysis to raise adverse events against placebo in travelers taking it for prevention, mostly nausea, bitter taste, diarrhea and dark stools.How often is not known
LimitedThe label warns children and teenagers who have or are recovering from chickenpox or flu-like symptoms not to use it, because of Reye's syndrome, a rare but serious illness.How often is not known
LimitedCase reports: heavy daily use caused salicylate poisoning with confusion, falls and hearing loss. The label warns people allergic to aspirin or taking other salicylates.How often is not known
LimitedCase reports: warfarin's effect rose with bismuth subsalicylate, with minor bleeding. The label tells people on blood thinners and drugs for diabetes, gout or arthritis to ask first.How often is not known
LimitedOne small study found the liquid form lowered tetracycline levels 27%, through a suspending agent rather than the bismuth itself.How often is not known
LimitedCase reports: years of use caused bismuth encephalopathy with confusion and jerking movements, which resolved after stopping. The Pylera label warns of neurotoxicity at excessive doses.How often is not known
LimitedThe Pylera label contraindicates use in pregnancy, mainly because of tetracycline, and states there are no human or animal data on its bismuth salt in pregnancy.How often is not known

What people take it for, and what was found

Shown to help4

Moderate

Preventing travelers' diarrhea

Shown to lower travelers' diarrhea in older trials, 14% on 2.1 g a day against 40% on placebo in Mexico. A small 2025 trial found no difference.

Compared with placebo [1][2][3][4]; rifaximin, probiotics and vaccines, in a network analysis [3]

The numbers and sources

Effect: Over 3 weeks, diarrhea occurred in 14% on 2 tablets four times a day, 24% on 1 tablet four times a day and 40% on placebo, protection rates of 65% and 40% [1]. Pooling 3 prevention studies, people on bismuth subsalicylate for up to 21 days had 3.5 times the odds of staying free of travelers' diarrhea (95% CI 2.1 to 5.9) [2]. In a network meta-analysis, travelers' diarrhea on bismuth subsalicylate was about a third of the placebo rate (RR 0.35, 95% CI 0.25 to 0.49), with moderate confidence [3]. In a 2025 trial of travelers to Asia and Africa taking 2.1 g a day, loose stool and diarrhea did not differ from placebo, and the trial did not reach its target size [4].
Population: 182 US students in Mexico [1]; 3 prevention studies from the 1970s to 2007 [2]; 31 trials with 10,879 participants, 209 on bismuth subsalicylate [3]; 270 adult travelers [4].
Sources: [1], [2], [3], [4]
Caveats: Graded Moderate, not Strong, though two reviews agree: both draw on the same older trials, and the one recent trial found no difference [4]. The over-the-counter label lists treatment, not prevention [5].

Moderate

Treating infectious and travelers' diarrhea

Shown to raise relief of infectious diarrhea against placebo, odds ratio 3.7, though loperamide cut unformed stools more in a head-to-head trial.

Compared with placebo [2]; loperamide [6]

The numbers and sources

Effect: Across 11 treatment studies, 5 of them in travelers' diarrhea, people on bismuth subsalicylate had 3.7 times the odds of diarrhea relief recorded in diaries (95% CI 2.1 to 6.3) [2]. Against loperamide in travelers, people on bismuth subsalicylate passed more unformed stools in every period through 48 hours, and fewer had constipation (1 against 8) [6]. An expert panel concluded that fluids alone, loperamide or bismuth subsalicylate may suffice for most mild travelers' diarrhea [7].
Population: 14 clinical studies in total, 11 on treatment [2]; 219 students traveling in Latin America [6]; an expert panel's appraisal [7].
Sources: [2], [6], [7]
Caveats: Relief was self-recorded. The pooled studies date from the 1970s to 2007 [2].

LimitedStudied in children

Diarrhea in infants and young children

Limited evidence: two trials in hospitalized infants found shorter diarrhea on bismuth subsalicylate with rehydration, ending within 5 days in 88% to 89% against 74% on placebo.

Compared with placebo [8][9]

The numbers and sources

Effect: Diarrhea stopped within 120 hours in 74% on placebo, 89% on 100 mg/kg a day and 88% on 150 mg/kg a day, with lower stool output and shorter hospital stays. Blood bismuth and salicylate stayed below toxic levels [8]. In a second trial, hospital stays were 6.9 days on bismuth subsalicylate and 8.5 days on placebo, with lower stool frequency and weight [9].
Population: 275 boys in Peru, mean age 13.5 months [8]; 123 children aged 4 to 28 months in hospital [9].
Sources: [8], [9]
Caveats: Hospitalized children on rehydration and feeding. The US over-the-counter label directs parents of children under 12 to ask a doctor, and warns against use in children and teenagers recovering from chickenpox or flu-like symptoms [5].

Moderate

H. pylori eradication, added to antibiotics

Shown to raise H. pylori eradication when bismuth was added to antibiotic regimens, odds ratio 1.83 overall and 2.81 as a simple add-on.

Compared with the same regimens without bismuth [10]; clarithromycin triple therapy [11]; a regimen with metronidazole in place of bismuth subsalicylate [12]

The numbers and sources

Effect: Across 25 trials, bismuth-containing first-line regimens raised eradication against regimens without bismuth (OR 1.83, 95% CI 1.57 to 2.13), and in 7 add-on trials the odds ratio was 2.81 (95% CI 2.03 to 3.89), with no significant rise in side effects [10]. Bismuth quadruple therapy eradicated H. pylori in 77.6% against 68.9% on clarithromycin triple therapy, not a significant difference overall (risk difference 0.06, 95% CI -0.01 to 0.13), but 10-day quadruple therapy beat 7-day triple therapy (risk difference 0.25, 95% CI 0.18 to 0.32) [11]. With bismuth subsalicylate 524 mg twice daily in place of metronidazole, eradication was 81% by intention to treat in both arms [12].
Population: 25 trials with 3,990 patients [10]; 12 trials [11]; 105 patients in one 7-day trial, 53 and 52 by intention to treat [12].
Sources: [10], [11], [12]
Caveats: The pooled trials used several bismuth salts, and Pylera uses bismuth subcitrate [13]. Heterogeneity in [11] was high (I² 78%). Only [12] tested bismuth subsalicylate itself.

Not shown to help1

Moderate

Upset stomach and indigestion

Not shown to ease non-ulcer dyspepsia against placebo in pooled trials of bismuth salts, a 40% risk reduction whose interval included no effect.

Compared with placebo [14]

The numbers and sources

Effect: Bismuth salts gave a relative risk reduction of 40% against placebo (95% CI -3% to 65%), which the review called of marginal statistical significance [14].
Population: 6 trials with 311 people with non-ulcer dyspepsia [14].
Sources: [14]
Caveats: The trials tested bismuth salts in general, not only bismuth subsalicylate. No trial of the label's overindulgence uses, such as heartburn, gas or fullness after a meal, was sourced [5].

Doses studied

The prevention trials used 2 tablets of 262 mg four times a day, 2.1 g a day, for up to 3 weeks, or 1 tablet four times a day [1], and 4 tablets twice a day in 2025 [4]. The over-the-counter liquid label gives 525 mg per 30 mL dose, every half hour or 60 mL every hour as needed for diarrhea, no more than 8 doses in 24 hours, and no more than 2 days [5]. The infant trials used 100 or 150 mg/kg a day for up to 5 days [8] and 20 mg/kg five times a day for 5 days [9]. The H. pylori trial used 524 mg twice a day for 7 days [12]. Pylera is 3 capsules four times a day for 10 days with omeprazole 20 mg twice a day [13].

Risks

Reported risks8

ModerateVery common

Black stool and dark tongue

Shown to darken stool, 15.6% on a bismuth regimen against 4.6% on a regimen without bismuth, and to darken the tongue. Labels describe it as temporary.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Dark stools were reported in 15.6% on omeprazole with Pylera and 4.6% on omeprazole, amoxicillin and clarithromycin, and tongue darkening in under 1%. The label states the darkening is temporary, reverses within several days and does not interfere with tests for blood in the stool [13]. Dark stools occurred in 23% on a bismuth subsalicylate regimen [12]. In the prevention trial, blackened tongue and stools were the most common side effects [1]. The over-the-counter label calls the darkening temporary and harmless [5].
Population: 147 and 152 patients in the North American H. pylori trial [13]; patients in a 7-day H. pylori trial [12]; 182 students [1].
Sources: [13], [12], [1], [5]
Caveats: Dark stool from bismuth can be mistaken for bleeding, and the over-the-counter label says not to use it if stool is already bloody or black [5].

ModerateHow often is not known

Side effects in travelers taking it for prevention

Shown in a network analysis to raise adverse events against placebo in travelers taking it for prevention, mostly nausea, bitter taste, diarrhea and dark stools.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: At the aggregate level, bismuth subsalicylate had a significantly higher adverse event rate than placebo. The authors list nausea, bitter taste, diarrhea and dark or black stools as the common events, usually mild [3]. Tinnitus occurred at 1.2 days per 100 days of treatment in one trial [1].
Population: Randomized prevention trials in travelers [3]; 182 students [1].
Sources: [3], [1]
Caveats: The parts of the review read for this page give no pooled adverse event rate [3].

LimitedHow often is not known

Reye's syndrome warning for children and teenagers

The label warns children and teenagers who have or are recovering from chickenpox or flu-like symptoms not to use it, because of Reye's syndrome, a rare but serious illness.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label carries a Reye's syndrome warning and states each 30 mL dose contains 261 mg of salicylate [5]. After a 60 mL dose, 95% of the salicylate was recovered in urine, so almost all is absorbed [15]. The link between salicylates and Reye's syndrome comes from aspirin, and a 2007 review argued that a cause and effect relationship is not supported by sufficient facts [16].
Population: Label statement [5]; 6 fasted men in an absorption study [15]; a narrative review [16].
Sources: [5], [15], [16]
Caveats: No study of Reye's syndrome after bismuth subsalicylate itself was sourced. In the infant trials, salicylate levels stayed below toxic levels [8].

LimitedHow often is not known

Salicylate toxicity and aspirin allergy

Case reports: heavy daily use caused salicylate poisoning with confusion, falls and hearing loss. The label warns people allergic to aspirin or taking other salicylates.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A 79-year-old man drinking 1 to 2 bottles a day had confusion, falls and hearing loss with a salicylate level of 2.08 mmol/L, and recovered after stopping [17]. Chronic salicylate toxicity from over-the-counter bismuth subsalicylate has also been reported [18]. The label says not to use it if allergic to salicylates, including aspirin, or if taking other salicylate products, and to stop if ringing in the ears or hearing loss occurs [5].
Population: Case reports [17][18]; label statements [5].
Sources: [17], [18], [5]
Caveats: Case reports give no rate.

LimitedHow often is not known

Blood thinners and other drugs

Case reports: warfarin's effect rose with bismuth subsalicylate, with minor bleeding. The label tells people on blood thinners and drugs for diabetes, gout or arthritis to ask first.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In a patient on warfarin, the INR rose from 2.56 to 3.54 within 3 days of starting bismuth subsalicylate, with minor bleeding, and settled after it was stopped. The authors judged the interaction probable, through salicylate displacing warfarin from blood proteins [19]. The over-the-counter label tells people taking drugs for anticoagulation, diabetes, gout or arthritis to ask a doctor or pharmacist first [5]. The Pylera label warns that it may alter warfarin's effect, through its metronidazole and tetracycline [13].
Population: One case report [19]; label statements [5][13].
Sources: [19], [5], [13]
Caveats: A single case. No controlled study was sourced.

LimitedHow often is not known

Lower tetracycline absorption

One small study found the liquid form lowered tetracycline levels 27%, through a suspending agent rather than the bismuth itself.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The liquid containing magnesium aluminum silicate lowered tetracycline peak levels 21% and total exposure 27%. A version without it lowered them 11% and 13%, not significantly [20].
Population: 11 healthy volunteers in a crossover study [20].
Sources: [20]
Caveats: Drug level study. The clinical relevance was not determined [20].

LimitedHow often is not known

Bismuth encephalopathy with long-term use

Case reports: years of use caused bismuth encephalopathy with confusion and jerking movements, which resolved after stopping. The Pylera label warns of neurotoxicity at excessive doses.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A 44-year-old woman who had used bismuth subsalicylate for about 20 years developed confusion, unsteadiness and myoclonus, with blood, urine and spinal fluid bismuth well above toxic thresholds, and recovered within weeks of stopping [21]. The Pylera label reports neurotoxicity with excessive doses of bismuth products, reversible when bismuth is stopped [13].
Population: Case report [21]; label statement [13].
Sources: [21], [13]
Caveats: Case reports give no rate.

LimitedHow often is not known

Use in pregnancy

The Pylera label contraindicates use in pregnancy, mainly because of tetracycline, and states there are no human or animal data on its bismuth salt in pregnancy.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The Pylera label contraindicates use in pregnancy because tetracyclines in the second and third trimesters can permanently discolor teeth and may affect bone development, and states there are no human or animal data on bismuth subcitrate potassium in pregnancy [13]. The over-the-counter label tells pregnant or breastfeeding women to ask a health professional first [5].
Population: Label statements [13][5].
Sources: [13], [5]
Caveats: No study of bismuth subsalicylate in pregnancy was sourced.

Possible, not studied in people1

Untested

FDA boxed warning on Pylera: cancer in animals

Not studied in people. Metronidazole, one of Pylera's three drugs, caused cancer in mice and rats, the basis of the label's boxed warning.

No study in people. This rests on animal studies.

The numbers and sources

Effect: The boxed warning states that metronidazole has been shown to be carcinogenic in mice and rats and that it is unknown whether it is linked to cancer in humans [13].
Population: Mice and rats given metronidazole [13].
Sources: [13]
Caveats: The warning concerns metronidazole, not bismuth, and over-the-counter bismuth subsalicylate carries no boxed warning [5].

Sources

DuPont HL, Ericsson CD, Johnson PC, et al. Prevention of travelers' diarrhea by the tablet formulation of bismuth subsalicylate. JAMA. 1987. https://doi.org/10.1001/jama.1987.03390100085031
Brum JM, Gibb RD, Ramsey DL, Balan G, Yacyshyn BR. Systematic Review and Meta-Analyses Assessment of the Clinical Efficacy of Bismuth Subsalicylate for Prevention and Treatment of Infectious Diarrhea. Digestive Diseases and Sciences. 2021. https://doi.org/10.1007/s10620-020-06509-7
Fan H, Liu IC, Gao L, Wu L. Bismuth subsalicylate, probiotics, rifaximin and vaccines for the prevention of travelers' diarrhea: a systematic review and network meta-analysis. Frontiers in Pharmacology. 2024. https://doi.org/10.3389/fphar.2024.1361501
Angelo KM, Salah Z, Rogova M, et al. Efficacy of bismuth subsalicylate on the prevention of travellers' diarrhoea, 2018 to 2023. Journal of Travel Medicine. 2025. https://doi.org/10.1093/jtm/taaf047
US Food and Drug Administration label. Pepto-Bismol (bismuth subsalicylate) suspension, Drug Facts. DailyMed. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=67006e82-870d-8d63-e053-2991aa0a02d1
Johnson PC, Ericsson CD, DuPont HL, et al. Comparison of loperamide with bismuth subsalicylate for the treatment of acute travelers' diarrhea. JAMA. 1986. https://doi.org/10.1001/jama.1986.03370060071021
Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report. Journal of Travel Medicine. 2017. https://doi.org/10.1093/jtm/tax026
Figueroa-Quintanilla D, Salazar-Lindo E, Sack RB, et al. A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease. New England Journal of Medicine. 1993. https://doi.org/10.1056/nejm199306103282301
Soriano-Brücher H, Avendaño P, O'Ryan M, et al. Bismuth subsalicylate in the treatment of acute diarrhea in children: a clinical study. Pediatrics. 1991. https://doi.org/10.1542/peds.87.1.18
Ko SW, Kim YJ, Chung WC, Lee SJ. Bismuth supplements as the first-line regimen for Helicobacter pylori eradication therapy: Systemic review and meta-analysis. Helicobacter. 2019. https://doi.org/10.1111/hel.12565
Venerito M, Krieger T, Ecker T, Leandro G, Malfertheiner P. Meta-analysis of bismuth quadruple therapy versus clarithromycin triple therapy for empiric primary treatment of Helicobacter pylori infection. Digestion. 2013. https://doi.org/10.1159/000350719
Chey WD, Fisher L, Elta GH, et al. Bismuth subsalicylate instead of metronidazole with lansoprazole and clarithromycin for Helicobacter pylori infection: a randomized trial. The American Journal of Gastroenterology. 1997. https://pubmed.ncbi.nlm.nih.gov/9317068/
US Food and Drug Administration label. Pylera (bismuth subcitrate potassium, metronidazole, and tetracycline hydrochloride) capsules. DailyMed. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5cdacbf5-67be-42eb-bd54-8acc32ea1abc
Moayyedi P, Shelly S, Deeks JJ, et al. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database of Systematic Reviews. 2006. https://doi.org/10.1002/14651858.cd001960.pub3
Feldman S, Chen SL, Pickering LK, et al. Salicylate absorption from a bismuth subsalicylate preparation. Clinical Pharmacology and Therapeutics. 1981. https://doi.org/10.1038/clpt.1981.112
Schrör K. Aspirin and Reye syndrome. Paediatric Drugs. 2007. https://doi.org/10.2165/00148581-200709030-00008
Halani S, Wu PE. Salicylate toxicity from chronic bismuth subsalicylate use. BMJ Case Reports. 2020. https://doi.org/10.1136/bcr-2020-236929
Vernace MA, Bellucci AG, Wilkes BM. Chronic salicylate toxicity due to consumption of over-the-counter bismuth subsalicylate. The American Journal of Medicine. 1994. https://doi.org/10.1016/0002-9343(94)90017-5
Bingham AL, Brown RO, Dickerson RN. Inadvertent exaggerated anticoagulation following use of bismuth subsalicylate in an enterally fed patient receiving warfarin therapy. Nutrition in Clinical Practice. 2013. https://doi.org/10.1177/0884533613507606
Healy DP, Dansereau RJ, Dunn AB, et al. Reduced tetracycline bioavailability caused by magnesium aluminum silicate in liquid formulations of bismuth subsalicylate. The Annals of Pharmacotherapy. 1997. https://doi.org/10.1177/106002809703101203
Borbinha C, Serrazina F, Salavisa M, Viana-Baptista M. Bismuth encephalopathy, a rare complication of long-standing use of bismuth subsalicylate. BMC Neurology. 2019. https://doi.org/10.1186/s12883-019-1437-9

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