Hepatitis C virus (HCV) infection is common among patients undergoing haemodialysis, and liver disease is an important cause of morbidity and mortality in this population. Management of HCV-related liver disease is a major health concern in patients with end-stage renal disease (ESRD) undergoing haemodialysis. To investigate the prevalence of HCV infection in patients on haemodialysis and its associated risk factors, we conducted a prospective case series study of 838 patients on haemodialysis in Tehran, Iran. Patients were selected randomly (cluster sampling) and all were screened for anti-HCV antibodies, using ELISA 3rd generation and confirmed by using RIBA 2nd generation. We found that 111 patients (13.2%) were infected. By applying univariate analysis, longer duration on haemodialysis (P = 0.000), more weekly dialysis sessions (P = 0.03), history of blood transfusion (P = 0.03) and history of previous renal transplantation (P = 0.01) were found to be associated with a higher rate of HCV infection. Multivariate analysis revealed that only length of time on dialysis (P = 0.000) and history of blood transfusion (P = 0.02) were significantly associated with HCV infection. The more the units transfused, the higher the rate of HCV infection. Our results suggest that early transplantation and avoidance of blood transfusion, as much as possible, are the two most important practical interventions to reduce the HCV exposure rate in our patients on haemodialysis.