The risk factors related to hepatitis C virus (HCV) infection showed geographic and temporal differences. We investigated HCV-related risk factors in Korea where intravenous drug use (IVDU) is uncommon. The HCV-related risk factors were investigated in a prospective, multicenter chronic HCV cohort (n = 711) using a standardized questionnaire in four university hospitals. The results were compared with those of 206 patients with chronic liver diseases not related to either of HCV or hepatitis B virus infection (comparison group). The IVDU was found in 3.9% and remote blood transfusion (≥ 20 yr ago) in 18.3% in HCV cohort group, while that in comparison group was in none and 5.3%, respectively. In a multivariate logistic analysis, transfusion in the remote past (odds ratio [OR], 2.99), needle stick injury (OR, 4.72), surgery (OR, 1.89), dental procedures (OR, 2.96), tattooing (OR, 2.07), and multiple sexual partners (2-3 persons; OR, 2.14, ≥ 4 persons; OR, 3.19), were independent risk factors for HCV infection. In conclusion, the major risk factors for HCV infection in Korea are mostly related to conventional or alterative healthcare procedures such as blood transfusion in the remote past, needle stick injury, surgery, dental procedure, and tattooing although multiple sex partners or IVDU plays a minor role.