We conducted a prospective cohort study of Nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer among 32,505 women in central Ohio, USA. After 5 years of follow-up, a total of 393 cases have been detected. The annual incidence of breast cancer per 100,00 women varied inversely with increasing intake of NSAIDs, declining from 323 among non-users to 183 among heavy users (p<0.01). Breast cancer rates decreased by about 50% with regular ibuprofen intake (p<0.01), and by about 40% with regular aspirin intake (p<0.05). The results suggest that specific NSAIDs may be effective chemopreventive agents against breast cancer.