We examined the association of nonsteroidal antiinflammatory drugs and breast cancer risk in a case-control study of 511 breast cancer patients and 1,534 population control subjects. The relative risk of breast cancer was reduced in women using these compounds at least 3 times per week for > or = 1 year [odds ratio (OR) = 0.66; 95% confidence interval (CI) = 0.52-0.83]. Odds ratios were similar for use of ibuprofen (0.57) or aspirin per se (0.69). Breast cancer risk declined with increasing exposure, and the greatest risk reduction (40%; odds ratio = 0.60; 95% CI = 0.40-0.91) occurred at the highest level of use (daily intake for > or = 5 years). These results indicate that nonsteroidal antiinflammatory drugs may have chemopreventive potential against the development of breast cancer.