In 1990-2002, the authors conducted a population-based cohort study of 2,447 Caucasian men in Olmsted County, Minnesota, to determine whether daily users of nonsteroidal antiinflammatory drugs (NSAIDs) were at lower risk than nondaily NSAID users of developing benign prostatic hyperplasia. Participants completed validated questionnaires during a home visit, including information about daily NSAID use. A random subset of 634 men also participated in a clinical evaluation including transrectal ultrasonography and assessment of serum prostate-specific antigen levels. Examinations and questionnaires were repeated biennially through 2002. Benign prostatic hyperplasia measures included development of moderate/severe urinary symptoms (American Urological Association Symptom Index score >7), low maximum urinary flow rate (<12 ml/second), prostate volume >30 ml, or prostate-specific antigen level >1.4 ng/ml. After adjustment for age, daily NSAID use was inversely associated with onset of moderate/severe urinary symptoms (hazard ratio (HR) = 0.73, 95% confidence interval (CI): 0.64, 0.82), low maximum flow rate (HR = 0.51, 95% CI: 0.43, 0.61), increased prostate volume (HR = 0.53, 95% CI: 0.41, 0.68), and elevated prostate-specific antigen level (HR = 0.52, 95% CI: 0.40, 0.68). In age-specific analyses, inverse associations between NSAID use and urinary measures tended to be stronger in the oldest age groups, although this interaction was statistically significant for only obstructive symptoms and treatment. Results suggest that NSAID use may prevent or delay development of benign prostatic hyperplasia.