The epidemiological and clinical features of hepatitis C virus (HCV) infection in South Korea were examined in a prospective, multicenter cohort study that included 1,173 adult patients with positive results for anti-HCV antibody who completed a questionnaire survey on the risk factors for HCV infection from January 2007 to December 2011 at five university hospitals. The HCV cohort had a mean age of 55.4 years with 48.3% men, and diagnostic categories of acute hepatitis (n = 63, 5.3%), past infection (n = 37, 3.2%), chronic hepatitis (n = 777, 66.2%), cirrhosis of the liver (n = 179, 15.3%), and hepatocellular carcinoma (n = 117, 10.0%). The major HCV genotypes were genotype 1 (52.7%) and genotype 2 (45.3%). Liver biopsy was performed in 301 patients (25.7%), and 42.8% of the subjects received antiviral therapy against HCV. The behavioral risk factors possibly related to HCV infection were intravenous drug use (5%), needle stick injury (7%), blood transfusion before 1995 (19%), sexual relationship with more than three partners (28%), piercings (35%), tattoos (36%), surgery (43%), acupuncture (83%), diagnostic endoscopy (85%), and dental procedures (93%). Age, intravenous drug use, needle stick injury, transfusion before 1995, and tattoos were the independent risk factors of HCV infection. J Med. Virol. 85:1724–1733, 2013. © 2013 Wiley Periodicals, Inc.