We examined the association of prostate cancer and non-steroidal anti-inflammatory drugs (NSAIDs) in a case control study of 417 prostate cancer patients and 420 group-matched control subjects. Regular daily use of over the counter NSAIDs, ibuprofen or aspirin, was associated with a 66% reduction in prostate cancer risk (odds ratio = 0.34, 95% confidence interval = 0.23-0.58, p<0.01). The risk of prostate cancer was also significantly reduced in men who reported taking prescription NSAIDs (odds ratio = 0.35, 95% confidence interval = 0.15-0.84, p<0.05). These results suggest that NSAIDs may have value in the chemoprevention of prostate cancer.