The association of nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk was examined in a case-control study of 303 breast cancer patients and 906 population control subjects. Breast cancer cases reported a significantly lower frequency of regular NSAID use than controls (19.1% versus 26.8%, p<0.01) and the resulting odds ratio adjusted for other risk factors was significantly less than 1 (OR=0.65, 95% CI=0.5-0.9, p<0.01). Regular intake of NSAIDs (greater than or equal to 3 times per week for greater than or equal to 6 months) was associated with a 36% reduction in the risk of breast cancer (OR=0.64, 95% CI=0.4-0.9, p<0.01). Greater use (greater than or equal to 7 times per week for greater than or equal to 5 years) resulted in a 40% risk reduction (OR=0.60, 95% CI=0.4-0.9, p<0.05). The observed effects of non-prescription and prescription NSAIDs were similar, although sample sizes were small for individual compounds. These results suggest that NSAIDs may have chemopreventive potential against the development of breast cancer.