Hepatitis C virus (HCV) infection is highly prevalent among chronic dialysis patients (10% to 40%) and is the most common cause of chronic liver disease. However, there are no studies estimating the risk for death among dialysis patients infected with HCV compared with those not infected. We conducted a prospective cohort study to estimate the risk for death among chronic dialysis patients infected with HCV compared with those not infected. In 1992, 200 patients (91%) who had been undergoing dialysis therapy for at least 6 months consented to be screened for HCV infection by enzyme immunoblot assay and polymerase chain reaction (PCR). Information about potential confounders and potential risk factors for death and HCV infection was obtained from the dialysis center database. Patient outcomes collected included death, transplantation, and loss to follow-up. The Cox proportional hazards model was used to estimate the odds of death among dialysis patients who were positive for the HCV antibody and HCV RNA compared with negative patients. Forty-four patients (22%) were HCV antibody positive. Thirty-four patients (17%) were HCV RNA positive. Patients in the HCV RNA-positive group were more likely to be younger (51.8+/-12.6 v 57.2+/-17.3 years of age), men (77% v 54%), and black (65% v 37%). None of the home hemodialysis or peritoneal dialysis patients were HCV RNA positive, whereas one of the home hemodialysis and one of the peritoneal dialysis patients were HCV antibody positive. Two patients became infected with HCV during the follow-up period. Patients who were HCV RNA positive and those who were HCV antibody positive were at increased risk for death compared with patients who were negative (adjusted relative risk [aRR]=1.78; 95% confidence interval [CI], 1.01 to 3.14; P=0.045; and aRR=1.97; 95% CI, 1.16 to 3.33; P=0.012, respectively), after adjusting for time on dialysis, race, transplantation, and age. We conclude that HCV infection increased the risk for death during the study period compared with those not infected. Further studies should assess the measures used to prevent and treat HCV infection.