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Introduction: The relative contributions of racial and environmental factors to the higher risk of stroke in people of African ancestry are not clear due to limited opportunities to evaluate stroke type and risk among indigenous Africans, in comparison with Africans in diaspora and their host populations. This knowledge could provide insights into avenues for similar vs. unique approaches to managing stroke risk in Africans.Objective: To compare the pattern of stroke and contribution of vascular risk factors to stroke among indigenous Africans, African Americans and European Americans.Methods: SIREN is a large multicenter case-control study involving several sites in West Africa, the ancestral home of 71% African Americans, whilst REGARDS is a cohort study including African and European Americans in the United States. Stroke diagnosis and type were confirmed using CT or MRI scan. Traditional vascular risk factors were assessed using history, physical examination and laboratory investigations. We compared data from acute stroke cases age≥55 years in SIREN and REGARDS in the distribution of key socio-demographic and clinical risk factors based on harmonized standard definitions.Results: There were 811 stroke subjects in the SIREN population (A) and 452 African Americans (B) and 665 European Americans (C) from the REGARDS study with a progressive increment in mean age of 68.0 ± 9.3, 73.0 ± 8.3 and 76.0 ± 8.3 years respectively, p<0.0001. Hemorrhagic stroke occurred in 291/811 (27.0%), 36/452 (8.0%) and 36/665 (5.4%), in A, B, and C (p < 0.001) respectively. There were significant differences in prevalence of vascular risk factors among the three groups namely hypertension: 92.8%, 82.5% & 64.2%, p<0.01; mean LDL cholesterol (mg/dl): 121±52, 116±32, 110±33 (p< 0.03); cardiac diseases: 12.5%, 25.0% & 31.7% (p< 0.01); sedentary lifestyle:8%, 37.7% and 34.0% (p<0.001); and 2.0%, 18.3% & 14.4% were current smokers in A, B and C respectively (p<0.001).Conclusion: Environmental risk factors such as cigarette smoking may contribute to the higher proportion of ischemic stroke in African-Americans compared to indigenous Africans, while racial factors may contribute to the higher proportion of hypertension among stroke subjects of African ancestry.