Coronary artery calcification (CAC) is prevalent and predicts mortality among patients with ESRD, but whether less severe kidney dysfunction is associated with CAC is uncertain. To address this question, 6749 participants of the Multi-Ethnic Study of Atherosclerosis, who were middle-aged and without known cardiovascular disease, were evaluated. Renal function was categorized by cystatin C quartiles and estimated GFR (eGFR; < to >60 ml/min per 1.73 m(2)), and CAC was evaluated by computed tomography (CT). Fifty percent of participants had CAC, mean cystatin C was 0.90 mg/L, and 10% had eGFR <60 ml/min per 1.73 m(2). In unadjusted analysis, kidney dysfunction by either measure was strongly associated with CAC; however, the associations were lost after adjustment for age, gender, race, hypertension, and IL-6 (relative risk 1.04 [95% confidence interval 0.97 to 1.11] for the highest cystatin C quartile compared with the lowest, and relative risk 1.03 [95% confidence interval 0.98 to 1.08] for eGFR below compared with above 60 m/min per 1.73 m(2)). Similarly, neither higher cystatin C nor eGFR <60 was associated with severity of CAC. These results suggest that a higher burden of CAC is unlikely to explain the association between mild to moderate kidney dysfunction and cardiovascular mortality.