Context: Aspirin use may reduce the risk of stroke and coronary heart disease. Differential use for vascular prophylaxis may contribute to racial and geographic disparities in stroke and coronary heart disease morbidity or mortality. Objective: To assess the prevalence and predictors of aspirin use for primary prophylaxis of stroke in the general population free of clinically diagnosed stroke or coronary heart disease. Design and setting: Cross-sectional analysis of 16,908 participants (age 45 or greater), from a population-based national cohort study (REasons for Geographic And Racial Differences in Stroke) enrolled from February 2003-August 2006 with oversampling from the southeastern Stroke Belt and African Americans. Individuals with a prior stroke or coronary heart disease, or regular use of aspirin for pain relief were excluded from analyses. Main outcome measures: Aspirin use and reasons for use were assessed using a computer-assisted telephone interview. Results: Prophylactic aspirin use was substantially higher among whites (34.7%) than African Americans (27.2%; p < 0.0001). There was a higher prevalence of aspirin use for prophylaxis in the Stroke Belt (32.1%) than in the rest of the nation (30.8%; p = 0.07). After adjustment for measures of socio-economic status, the odds ratio of aspirin use in the rest of the nation compared to Stroke Belt was 0.90 (95% CI 0.84-0.97). There was a higher likelihood of prophylactic aspirin use among participants who were white, male, older, past cigarette smokers, or of higher socio-economic status (higher income or education). Conclusions: In this study, aspirin use to prevent stroke and coronary heart disease was higher among whites than African Americans, raising the possibility that differential aspirin use could contribute to the racial disparities in vascular disease mortality. Counter to our hypothesis, aspirin use was more common in the Stroke Belt than the rest of the country, so differential aspirin use in the Stroke Belt is unlikely to contribute to geographic disparities in stroke. © 2008 Elsevier Inc. All rights reserved.