Objectives: To examine associations between specific inflammatory biomarkers and cognitive function in African Americans (AAs) and European Americans (EAs) with prevalent vascular risk factors., Design: Cross-sectional analysis using generalized estimating equations to account for familial clustering; standardized β-coefficients, adjusted for age, sex, and education are reported., Setting: Community cohort study in Jackson, Mississippi, and Rochester, Minnesota., Participants: Genetic Epidemiology Network of Arteriopathy (GENOA)-Genetics of Microangiopathic Brain Injury (GMBI) Study participants., Measurements: Associations between inflammation (high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, soluble tumor necrosis factor (TNF) receptor 1 and 2 (sTNFR1, sTNFR2)) and cognitive function (global, processing speed, language, memory, and executive function) were examined in AAs and EAs (N = 1,965; aged 26-95, 64% women, 52% AA, 75% with hypertension)., Results: In AAs, higher sTNFR2 was associated with poorer cognition in all domains (global: -0.11, P = .009; processing speed: -0.11, P < .001; language: -0.08, P = .002; memory: -0.09, P = .008; executive function: -0.07, P = .03); sTNFR1 was associated with slower processing speed (-0.08, P < .001) and poorer executive function (-0.08, P = .008); higher CRP was associated with slower processing speed (-0.04, P = .024), and higher IL6 was associated with poorer executive function (-0.07, P = .02). In EA, only higher sTNFR1 was associated with slower processing speed (-0.05, P = .007). Associations were not found between cognition and sTNFR2, CRP, or IL6 in EA., Conclusion: In a population with high vascular risk, adverse associations between inflammation and cognitive function were especially apparent in AAs, primarily involving markers of TNFα activity., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)