Background: Hepatitis C is more prevalent in patients with end-stage renal disease (ESRD) than in the general population. Previously, infection from nosocomial sources was an important cause for this increase. In the past decade, the risk from these sources has lessened, but the estimated percentage of patients with ESRD with hepatitis C virus (HCV) antibody (anti-HCV) has not changed. Methods: This is a prospective observational study of hemodialysis patients in 4 urban units in Birmingham, AL. Testing for anti-HCV was performed at the initiation of dialysis therapy and then yearly from August 1998 through August 2004. Race, sex, age, ESRD date, comorbid conditions, and outcomes were recorded. Results: The prevalence of anti-HCV was 16.8% in 860 patients (89% black). Patients new to ESRD had a prevalence of 14.4%. Seroconversion in previously anti-HCV-negative patients was 2.5%. Anti-HCV occurred in black men 3 times more than in black women (odds ratio, 3.3; 95% confidence interval, 2.2 to 5.0). Mean age at ESRD was significantly younger in anti-HCV-positive than HCV-negative patients (47.3 versus 54.1 years; P < 0.0001). Age, race, sex, and history of drug abuse were predictors of anti-HCV positivity. Conclusion: The prevalence of anti-HCV among patients with ESRD varies from community to community. New patients are major contributors to the prevalence of anti-HCV in patients with ESRD, particularly those who are younger, male, black, or have a history of drug use. Measuring anti-HCV levels in patients with chronic kidney disease may help identify those at risk for additional disorders. © 2005 by the National Kidney Foundation, Inc.