Epidemiologic data on the association between nonsteroidal antiinflammatory drugs (NSAIDs) and ovarian cancer risk have been inconsistent. The authors prospectively examined the association between regular use of aspirin and nonaspirin NSAIDs and ovarian cancer incidence among 197,486 participants of the Nurses' Health Study (NHS) and the Nurses' Health Study-II (NHS-II) over 24 and 16 years of follow-up, respectively. Information on aspirin was initially assessed in 1980 (NHS) and 1989 (NHS-II) and on nonaspirin NSAIDs and acetaminophen in 1990 (NHS) and 1989 (NHS-II) and updated throughout follow-up. The authors used Cox proportional hazards models adjusting for ovarian cancer risk factors. A total of 666 confirmed cases of epithelial ovarian cancer were identified over 2,790,986 person-years of follow-up. The hazard ratios associated with regular use of aspirin, nonaspirin NSAIDs, and acetaminophen were 1.11 (95% confidence interval (CI): 0.92, 1.33), 0.81 (95% CI: 0.64, 1.01), and 1.14 (95% CI: 0.92, 1.43), respectively. The authors did not observe a dose-response relation with increased frequency or duration of regular use of any of these medications and ovarian cancer incidence. The results did not differ substantially by tumor histology. In this large prospective study, the authors found no compelling evidence to support an association between regular use of aspirin, nonaspirin NSAIDs, or acetaminophen and ovarian cancer incidence.