The impact of hepatitis C virus (HCV) and other comorbid conditions upon survival is not well quantified in patients on dialysis. We identified HCV-infected and uninfected persons in the USRDS using claims data in 1997-1998 and followed until September 22, 2002 or death. We used Gray's time-varying coefficients model to examine factors associated with survival. Subjects with a renal transplant were excluded. A total of 5737 HCV-infected and 11 228 HCV-uninfected persons were identified. HCV-infected subjects were younger (mean age 57.8 vs 65.3 years), more likely to be male (57.6%vs 49.6%) and black (54.0%vs 36.4%). They were more likely to have a diagnosis of drug (16.5%vs 4.6%) and alcohol use (14.0%vs 3.1%), and to be human immunodeficiency virus (HIV) co-infected (7.4%vs 1.8%) (all comparisons, P < 0.0005). In an adjusted Gray's time-varying coefficient model, HCV was associated with an increased risk of mortality (P < 0.0005). The hazards were highest at the time of HCV diagnosis and decreased to a stable level 2 years after diagnosis. Other factors associated with increased risk of mortality were (P < 0.0005 unless stated) HIV coinfection; diagnosis of drug use (P = 0.001); coronary artery disease (P = 0.006); stroke; diabetes as the primary cause for renal failure; peripheral vascular disease; depression and presence of anaemia. HCV was associated with higher risk of death in patients on dialysis, even after adjusting for concurrent comorbidities. The risk was highest at the time of HCV diagnosis and stabilized over time. Clinical trials of HCV screening and treatment to reduce mortality in this population are warranted.