OBJECTIVES: To examine the impact of biological, psychosocial and other socioeconomic risk factors on incident stroke and to estimate the population attributable risk (PAR) of factors associated with stroke in African Americans enrolled in the Jackson Heart Study (JHS). METHODS: This is a nested case-control study of a cohort of African Americans enrolled in the JHS. Cases were patients with incident stroke during a 10 Year follow up period. Five controls were selected for each case using incidence density sampling and matched with cases on person-years spent in the cohort. Odds ratios (OR) and PARs were calculated to understand the impact of different risk factors on incident stroke. RESULTS: From a cohort of 5,302 patients, 129 cases of incident stroke and 590 controls were identified. Hypertension and diabetes were found to be the two strongest risk factors of stroke, with an OR of 1.8 (95% CI 1.1 - 3.1) for hypertension and 1.7 (95% CI 1.1 - 2.7) for diabetes, followed by the Framingham stroke risk score, where the risk of stroke increased by 4% for every 1% increase in the Framingham stroke risk score (OR 1.04, 95% CI 1.01 - 1.08). Psychosocial risk factors including depression (OR 0.7, 95% CI 0.4-1.2), stress (OR 0.9, 95% CI 0.9-1.0), and major life events (OR 1.0, 95% CI 0.9-1.1), were not significantly associated with incident stroke in this population. The overall PAR for biological and psychosocial risk factors combined accounted for 77.5% of incident stroke. CONCLUSIONS: African Americans with hypertension and diabetes were at a higher risk of developing stroke. However, findings on the association between depression and stroke were somewhat inconsistent with previous JHS studies due to the way depression was measured.