BACKGROUND AND PURPOSE: The most well-known stroke risk score is the Framingham Stroke Risk Score (FSRS), which was developed during the higher stroke risk period of the 1990s and has not been validated for blacks. We assessed the performance of the FSRS among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine whether it is useful in both blacks and whites. METHODS: Expected annualized stroke rates from the FSRS were compared with observed stroke rates overall and within strata defined by FSRS risk factors (age, sex, systolic blood pressure, use of antihypertensive medications, diabetes mellitus, smoking, atrial fibrillation, left ventricular hypertrophy, and prevalent coronary heart disease). RESULTS: Among 27 748 participants stroke-free at baseline, 715 stroke events occurred over 5.6 years of follow-up. FSRS-estimated incidence rates of stroke were 1.6× higher than observed for black men, 1.9× higher for white men, 1.7× higher for black women, and 1.7× higher for white women. This overestimation was consistent among most subgroups of FSRS factors, although the magnitude of overestimation varied by the risk factor assessed. CONCLUSIONS: Although higher FSRS was associated with higher stroke risk, the FSRS overestimated the observed stroke rates in this study, particularly in certain subgroups. This may be because of temporal declines in stroke rates, secular trends in prevention treatments, or differences in populations studied. More accurate estimates of event rates are critical for planning research, including clinical trials, and targeting health-care efforts.