INTRODUCTION: Bile acids have been implicated in gastric carcinogenesis. We hypothesized that bile acid sequestrant medication (BAM) use is associated with a lower gastric cancer (GC) incidence. METHODS: We assembled a cohort of veterans receiving longitudinal care within the Veterans Health Administration between 2000 and 2020 who completed testing for Helicobacterpylori . The index date was the date of completed H. pylori testing. The primary exposure was the number of filled BAM prescription(s) in the 5 years before the index date. The primary outcome was incident GC, stratified by anatomic subsite. Follow-up began at the index date and ended at the earliest of GC, death, after 2 years of follow-up, or the study end (May 31, 2020). We used Kaplan-Meier curves to visualize differences in GC incidence by exposure group and multivariable Cox proportional hazards models to estimate the association between BAM exposure and anatomic site-specific GC. RESULTS: Among 417,239 individuals (89% male, mean age 54 years, 63% non-Hispanic White), 4,916 (1.2%) filled at least one BAM prescription, 2,623 of whom filled ≥4. Compared with unexposed individuals, those with ≥4 BAM fills before entry had a lower incidence (adjusted hazard ratio 0.71; 95% confidence interval, 0.37-1.36) of GC, but confidence intervals were wide. Results were consistent irrespective of GC anatomic site. DISCUSSION: BAMs may have a protective effect against both cardia and noncardia GC. Further research and external validation are needed to confirm these findings.