OBJECTIVE: To examine vascular risk factors, as measured by the Framingham Stroke Risk Profile (FSRP), to predict incident cognitive impairment in a large, national sample of black and white adults age 45 years and older. METHODS: Participants included subjects without stroke at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with at least 2 cognitive function assessments during the follow-up (n = 23,752). Incident cognitive impairment was defined as decline from a baseline score of 5 or 6 (of possible 6 points) to the most recent follow-up score of 4 or less on the Six-item Screener (SIS). Subjects with suspected stroke during follow-up were censored. RESULTS: During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment. Baseline FSRP score was associated with incident cognitive impairment. An adjusted model revealed that male sex (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.43-1.77), black race (OR = 2.09, 95% CI 1.88-2.35), less education (less than high school graduate vs college graduate, OR = 2.21, 95% CI 1.88-2.60), older age (10-year increments, OR = 2.11, per 10-year increase in age, 95% CI 2.05-2.18), and presence of left ventricular hypertrophy (LVH, OR = 1.29, 95% CI 1.06-1.58) were related to development of cognitive impairment. When LVH was excluded from the model, elevated systolic blood pressure was related to incident cognitive impairment. CONCLUSIONS: Total FSRP score, elevated blood pressure, and LVH predict development of clinically significant cognitive dysfunction. Prevention and treatment of high blood pressure may be effective in preserving cognitive health.