Supplementation with antioxidant vitamins has been associated with decreased risk of stomach cancer or regression of precancerous lesions in high-risk areas of China and Colombia. We examined the association between stomach cancer mortality and regular use (> or =15 times per month) of individual vitamin C supplements, individual vitamin E supplements, and multivitamins among 1,045,923 United States adults in the Cancer Prevention Study II (CPS-II) cohort. CPS-II participants completed a questionnaire at enrollment in 1982 and were followed for mortality through 1998. During follow-up, there were 1,725 stomach cancer deaths (1,127 in men and 598 in women). After adjustment for multiple potential stomach cancer risk factors, vitamin C use at enrollment was associated with reduced risk of stomach cancer mortality [rate ratio (RR), 0.83; 95% confidence interval (CI), 0.68-1.01]. However, this reduction in risk was observed only among participants with short duration use at enrollment (RR, 0.68; 95% CI, 0.51-0.91 for <10 years of use; RR, 1.00; 95% CI, 0.73-1.38 for > or =10 years of use). There was no association between stomach cancer mortality and regular use of vitamin E (RR, 1.02; 95% CI, 0.82-1.27) or multivitamins (RR, 0.89; 95% CI, 0.77-1.03), regardless of duration of use. Our results suggest that the use of vitamin C, vitamin E, or multivitamin supplements may not substantially reduce risk of stomach cancer mortality in North American populations in which stomach cancer rates are relatively low. Our results do not rule out effects of vitamin supplementation in areas in which stomach cancer rates are high and stomach cancer etiology may differ.