Background: Although many experimental, epidemiologic, and clinical studies have suggested that aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in reducing and preventing colorectal adenomas, randomized, controlled trials (RCTs) are still being carried out to obtain statistically reliable results. Objective: The aim of this meta-analysis was to review long-term, prospective RCTs investigating the effect of NSAIDs on the relative risk (RR) for developing 1 new colorectal polyp or adenoma in a high-risk population. Methods: We conducted a comprehensive search of MEDLINE, PubMed, and other electronic databases (including Inter-Science, Science Direct, Ebsco, Synergy, and Proquest) (key terms: nonsteroidal anti-inflammatory drugs, aspirin, colorectal, and polyps; years: 1974-2004) for English-language articles. Eligible studies were analyzed in terms of demographic data, adverse effects, and effect of NSAIDs on the RRs. Results: Four long-term, prospective RCTs were used in the statistical analysis. A total of 2069 high-risk patients were enrolled; 1880 patients completed the studies, and 1127 were in active-treatment groups (aspirin 81-325 mg/d or sulindac 150-300 mg/d). Our meta-analysis of these studies revealed that the overall RR for developing 1 new colorectal polyp or adenoma was significantly reduced by using aspirin or other NSAIDs (RR = 0.809; 95% CI, 0.718-0.912). Conclusions: The results of this meta-analysis suggest that regular use of aspirin 81 to 325 mg/d or sulindac 150 to 300 mg/d for greater than or equal to1 year was associated with a decrease in the RR for developing greater than or equal to1 new colorectal polyp or adenoma to 0.80 (95% CI, 0.718-0.912) in patients at high risk. Copyright (C) 2004 Excerpta Medica, Inc.