Aspirin and/or non-aspirin NSAID use is thought to reduce the risk of several cancers, but studies in pancreatic cancer with animals and patients have yielded conflicting results regarding the relationship of these drugs. Now, in a pooled analysis of two large prospective cohorts (n = 141,940) from the Health Professionals Follow-up Study and the Nurses' Health Study, no association was identified between regular aspirin and/or non-aspirin NSAID use and the incidence of pancreatic cancer. Several analytical approaches were used to account for a range of time periods between NSAID use and the development of cancer, but the lack of association was consistent. However, in a subgroup analysis, regular aspirin use was associated with reduced pancreatic cancer risk among participants with diabetes mellitus (relative risk, 0.71; 95% CI 0.54–0.94).