The aim of this study was to investigate the association of C-reactive protein (CRP) with the metabolic syndrome (MS) and its components, and their association with coronary artery disease (CAD) in African Americans and European Americans. MS was defined using revised National Cholesterol Education Program Adult Treatment Panel III criteria in 224 African Americans and 304 European Americans who underwent coronary angiography; CAD was defined as > or =50% stenosis in any segment or as a composite cardiovascular score (0 to 75). The relative frequencies of MS and CAD were significantly higher in African Americans with high (> or =3 mg/L) versus low (<3 mg/L) CRP levels (76% vs 24%, p <0.001, for MS and 70% vs 30%, p = 0.001, for CAD). Composite scores were higher in subjects with high (> or =3 mg/L) versus low (<3 mg/L) CRP levels in African Americans (16.9 vs 11.2, p = 0.038) and European Americans (18.5 vs 14.5, p = 0.002). Furthermore, in the 2 ethnic groups, cardiovascular scores were higher in subjects with MS, irrespective of CRP levels. Adjusting for other risk factors, multiple regression analysis demonstrated an association of MS, but not CRP, with CAD in European Americans but not African Americans (r(2) = 0.533, p <0.001). In conclusion, MS was independently associated with CAD in European Americans and African Americans, whereas CRP did not add prognostic information beyond established cardiovascular risk factors in either ethnic group.