Objectives: African Americans (AA) have higher risk for coronary heart disease (CHD) outcomes than Whites. This racial disparity has been attributed to differences in risk factors such as hypertension, diabetes, smoking, and inactivity. Depression has been associated with CHD risk, both through behavioral factors and possibly through more direct mechanisms. Yet, the role of depressive symptoms in racial disparities in risk of CHD is not clear. Using the REGARDS Study, we examined the association between depressive symptoms and incident CHD. Hypothesis: Depressive symptoms are associated with incident CHD among AA, but not Whites. Methods: REGARDS is a national cohort of US community-dwelling adults aged >45 recruited from 2003 to 2007. Longitudinal associations of depressive symptoms with incident acute CHD (fatal CHD or nonfatal myocardial infarction or coronary revascularization) by race were examined among 24,261 participants (AA = 10,265; Whites =13,996) free of CHD at baseline, and observed through 12/31/09. Baseline depressive symptoms were defined by the 4-item Centers for Epidemiological Studies Depression Scale (CES-D), with continuous scores (0-12 range) dichotomized as normal (<4) or depressive symptoms (≥4). We estimated multivariable Cox proportional hazards models of incident CHD with depressive symptoms, adjusting for sociodemographics, CHD risk factors and health behaviors. Results: Overall mean follow-up was 4.2+1.5 years, CHD incidence was 8.3 events per 1000 person-years (n=366 events) among AA and 8.8 events per 1000 person-years (n=613 events) among Whites, p=0.0015. Depressive symptoms were more prevalent among AA (13.1%) than among Whites (8.5%), p<0.001. There was a significant interaction between race and depressive symptoms, thus models were stratified on race. After adjustment for age, sex, marital status and region, depressive symptoms were significantly associated with incident CHD among AA (HR 1.57 {95% CI 1.18-2.09}) but not among Whites (HR 1.11 {0.80-1.56}). After adding education, income, physical activity, smoking, alcohol consumption, diabetes, BMI, CRP, systolic blood pressure, cholesterol, albuminuria, use of blood pressure or statin medications, the relationship for AA was modestly attenuated but still significant (HR 1.35 {95% CI 1.01-1.81}). Conclusions: Depressive symptoms were associated with risk of incident CHD among AA but not Whites. Efforts to reduce racial disparities in CHD may need to address environmental and psychosocial factors that place AA at higher risk.