The association of hepatitis C virus (HCV) infection with chronic kidney disease (CKD) remains widely debated. Here we quantify this association by analysis of data from the Taiwan National Health Insurance Research Database and ICD-9 codes to identify 9430 adults with newly diagnosed HCV (years 1999-2006) and randomly selected 37,720 matched non-HCV control individuals. The incidence rate and risk of incident CKD were evaluated through the end of 2010. The frequency of CKD was 1.66-fold higher in the HCV than the non-HCV cohort (5.46 compared with 3.43 per 1000 person-years), and the adjusted hazard ratio remained significant at 1.28 (95% confidence interval, 1.12-1.46). A multivariate analysis was used to determine the influence of HCV on CKD risk with regard to age, gender, follow-up duration, and comorbidities. The risk for CKD in HCV-infected individuals was higher with diabetes, hyperlipidemia, and cirrhosis (8.44; 3.70-19.23), followed by men<50 years (2.32; 1.49-3.61), all individuals<50 years (1.90; 1.33-2.73), men overall (1.44; 1.22-1.71), and individuals followed for ≥6 years (1.35; 1.06-1.71); all with considerable significance. Thus, HCV infection is associated with an increased risk of CKD. Hence, high-risk HCV-infected individuals should be aggressively monitored for development of CKD.