We conducted a case-control study at Group Health Cooperative of Puget Sound to evaluate the relation between longterm histamine-2 (H2) receptor antagonist use and gastric cancer. We identified 113 cases and 452 controls and estimated a relative risk (RR) of 2.0 [95% confidence interval (CI) = 1.0-3.9]. When we evaluated the effect of time-since-first-use, the RR estimates were 6.5, 1.2, and 1.0 for 2-4 years of use, 5-9 years, and ≥10 years, respectively. The data provide substantial evidence that long-term H2 antagonist use is not associated with gastric cancer.