Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce dopaminergic neuron degeneration in animal models of Parkinson disease (PD). However, no epidemiological data have been available on NSAID use and the risk of PD. To investigate prospectively whether the use of nonaspirin NSAIDs or aspirin is associated with decreased PD risk. Prospective cohorts of 44 057 men and 98 845 women free of PD, stroke, or cancer (Health Professionals Follow-up Study, 1986-2000, and Nurses' Health Study, 1980-1998). Main Outcome Measure Newly diagnosed PD. We documented 415 incident PD cases (236 men and 179 women). Participants who reported regular use of nonaspirin NSAIDs at the beginning of the study had a lower risk of PD than nonregular users during the follow-up; the pooled multivariate relative risk was 0.55 (95% confidence interval, 0.32-0.96, P =.04). Compared with nonusers, a nonsignificantly lower risk of PD was also observed among men and women who took 2 or more tablets of aspirin per day (relative risk, 0.56; 95% confidence interval, 0.26-1.21). These findings are consistent with the hypothesis that use of NSAIDs may delay or prevent the onset of PD.