The temporal relation of hepatitis C virus (HCV) infection to the development of type 2 diabetes remains unknown. The authors followed 4,958 persons aged > or =40 years without diabetes (3,486 seronegative, 812 anti-HCV+, 116 with hepatitis B virus/HCV coinfection, and 544 hepatitis B surface antigen (HBsAg)+) from a community-wide cohort in southern Taiwan for 7 years (1997-2003) to study the risk of diabetes associated with HCV infection. A total of 474 participants developed diabetes. The 7-year cumulative incidence was 7.5% for HBsAg+, 8.6% for seronegative, 14.3% for anti-HCV+, and 14.7% for coinfected participants. Compared with HCV- persons, HCV+ persons had a higher cumulative incidence of diabetes (log-rank test, p < 0.0001). A multivariate Cox proportional hazards model showed that anti-HCV+ (hazard ratio = 1.7, 95% confidence interval: 1.3, 2.1), coinfection (hazard ratio = 1.7), overweight, obesity, and increasing age were significantly associated with diabetes (p < 0.05). Gender, educational level, HBsAg+ status, alcohol consumption, and smoking were not significant. After stratification by age and body mass index, the risk ratio for diabetes in anti-HCV+ participants increased when age decreased and body mass index levels increased (p < 0.001). Results show that HCV infection is an independent predictor of diabetes, especially for anti-HCV+ persons who are younger or have a higher body mass index.