The objective of the study was to assess the association between aspirin use and the risk of stroke in a population-based study in the elderly. The study was carried out within the framework of the Rotterdam Study, a prospective population-based cohort study. In the total study population there was a weak, nonsignificant association between aspirin use and the risk of stroke (adjusted relative risk 1.29, 95% CI 0.91-1.83). Stratification by history of vascular diseases revealed that aspirin considerably increased the risk of first-ever stroke in subjects free from vascular disease (adjusted relative risk 1.80; 95% CI 1.03-3.13). In persons with vascular disease, no association was observed between aspirin use and risk of stroke (adjusted relative risk 0.99, 95% CI 0.56-1.73). Our findings suggest that aspirin use may increase the risk of stroke in elderly subjects free from vascular disease.