To determine the incidence rate of cardiovascular disease (CVD) and its association with conventional and less well-established risk factors in African Americans with diabetes, we studied 741 African Americans aged 45 to 64 years with diabetes, in the Atherosclerosis Risk in Communities (ARIC) study. Risk factors were measured from 1987 to 1989, and incident CVD (n = 143 coronary heart disease (CHD) or stroke events) was ascertained through 1998. The crude incidence rate (per 1000 person-years) of CVD was 22.5 (11.9 for CHD and 12.0 for stroke). After multivariate adjustments, total cholesterol, prevalent hypertension and current smoking were significantly and positively associated with incident CVD among these African Americans with diabetes. Among the non-conventional risk factors, serum creatinine, factor VIII, von Willebrand factor, and white blood cell count were positively and serum albumin negatively and independently associated with CVD incidence. Adjusted relative risks for highest versus lowest tertiles of these risk factors ranged from 1.77 to 2.13. This study confirms that the major risk factors (hypercholesterolemia, hypertension and smoking) are important determinants of CVD in African Americans with diabetes. In addition, several blood markers of hemostasis or inflammatory response and elevated serum creatinine also proved to be CVD risk factors in African Americans with diabetes.