There are many publications to date confirming the significant association of HCV in the aetiology of chronic liver disease (CLD) world wide. Unfortunately information on the prevalence of HCV infection is sparse in Nigeria. This case controlled study was set to evaluate the prevalence of HCV infection in Nigerians with chronic liver disease and to determine the relative association of certain risk factors such as blood transfusion, traditional surgical practices, alcohol ingestion and the presence of hepatitis B surface antigen (HBS Ag) in the frequency of HCV related liver disease. The study was conducted at the Medical Department of the University of Maiduguri Teaching Hospital between August 2006 and May 2007. Ninety CLD patients who satisfied the inclusion criteria completed the study while 85 patients with non-hepatitis disease and healthy age-matched volunteers served as the controls. All subjects were tested for HCV antibodies using third generation EIA. Anti-HCV was detected in 14.4% and 2.4% of patients and controls respectively (p<0.05). There was a significant association between HCV and HBV (p<0.05). Previous blood transfusion and traditional surgical practices were significant risk factors for the acquisition of HCV in most of the patients. It is concluded that the prevalence of anti-HCV is high in Maiduguri and the risk of HCV infection increased significantly in CLD patients who had received blood transfusion/traditional surgical practices. The results provide significant evidence of an association between HBV and HCV. It is suggested that the risk of HCV infection may be minimized by screening of blood product to be transfused for anti HCV and avoiding traditional practices such as therapeutic scarification, uvulectomy and tattooing.