Background: Hepatitis C Virus (HCV) infection is a public health problem worldwide, with particular relevance in multi-transfusedpatients given that HCV is principally transmitted by exposure to infected blood. Study design: Between February and September 2003 a cross-sectional study was carried out in four hospital centres in Bogotá and Medellin, Colombia, to determine the risk factors for HCV infection in 500 multi-transfused patients. Results: The study population was distributed in five groups: haemophilia, haemodyalsis, acute bleeding, ontological illnesses and sickle cell disease or thalassemia. Serum samples from patients were tested for HCV antibodies (Asxym™, Abbott). An overall prevalence (9.0%; 95% confidence interval (CI): 6.4-11.6) (45/500) of HCV infection was found. Anti-HCV antibodies were detected in 32.2% of patients with haemophilia, 6.1% of patients undergoing haemodialysis, 7.1% of patients with sickle cell disease or thalassemia, 2.6% of patients with acute bleeding and 3.4% of patients with ontological or hematological diseases. The main risk factors associated with infection by HCV were: to be hemophilic (odds ratio, OR = 18.03; 95% Cl: 3.96-114.17), havingreceived transfusions before 1995 (OR = 12.27; 95% Cl: 5.57-27.69), and having received more than 48 units of blood components (OR = 6.08; 95% CI: 3.06-12.1). In the multivariate analysis, only the year of transfusions (before 1995) remained significantly associated with risk of infection by HCV. Conclusions: The data show a 3-fold reduction in the infection risk between 1993 and 1995, when the serological screening for HCVin blood donors was being introduced. A reduction greater than 90% was achieved by 1995 when the screening coverage reached 99%.