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Objective Systemic inflammation has been implicated as an early marker for subclinical cardiovascular disease; however, findings have been inconsistent in the African American population. Methods We examined the relation of C-reactive protein to subclinical disease in African American participants of the Jackson Heart Study first examination. Subclinical disease evaluated included aortic valve calcification (AVC), carotid intima-medial thickness (IMT) and peripheral arterial disease (PAD). We assessed the relation of C-reactive protein to subclinical disease adjusting for age, body mass index, sex, systolic and diastolic blood pressure, diabetes, total/HDL cholesterol, triglycerides, smoking, antihypertensive therapy, lipid lowering therapy, and hormone replacement therapy. Results In the study population approximately, 5.1% of participants had AVC and 6.7% had PAD. In the age- and sex- adjusted model, CRP was significantly related to AVC (p=0.02) and carotid IMT (p=0.02). However, in the multivariable-adjusted logistic regression analysis, C-reactive was significantly related to AVC (p=0.02) and to PAD (p=0.04) but not to carotid IMT (p=0.18). Conclusion We describe significant associations between C-reactive protein and AVC and PAD in a population-based cohort of African Americans.