Most epidemiological evidence supports the inverse association between use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) and colorectal cancer. Few studies have investigated the relation between use of aspirin and other NSAIDs and adenomatous polyps, which are recognized as precursors of colorectal cancer. We examined the association of adenomatous polyps and the dose and duration of use of aspirin and other NSAIDs in a case-control study of dietary risk factors for colorectal adenomatous polyps. The study population comprised 157 case and 480 control individuals who underwent an endoscopy at collaborating gastroenterology clinics in Houston, TX. Face-to-face interviews were conducted to obtain risk factor data that included information on frequency and duration of use of aspirin and other NSAIDs. Compared to the nonusers, the multivariate odds ratios for individuals who took aspirin and other NSAIDs on a weekly basis and for those who took these once/day or more were 0.77 (95% confidence interval, 0.39-1.55) and 0.36 (95% confidence interval, 0.20-0.63), respectively. Compared to the nonusers, the odds ratio for individuals who used aspirin and other NSAIDs for <5 years was 0.39 (95% confidence interval, 0.39-1.55) and 0.36 (95% confidence interval, 0.20-0.71), and for those who used these for 5 years or more, the odds ratio was 0.60 (95% confidence interval, 0.32-1.14). The results of this study suggest that aspirin and other NSAIDs are associated with a decreased risk for adenomatous polyps. Limited dose-response analyses found that the point estimate decreased with the frequency but not the duration of use of aspirin and other NSAIDs.