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Several previous studies have reported a high prevalence of hepatitis C virus (HCV) infection among commercial sex workers (CSWs), but the situation is often compounded by coexisting factors, such as intravenous drug use. We conducted a seroepidemiologic study of 1,527 female CSWs in South Korea. All participants tested negative for human immunodeficiency virus and were not illicit intravenous drug users (IDUs). Twenty-one participants (1.4%) were positive for antibodies to HCV. According to the multivariate logistic regression analysis, a history of acupuncture and diabetes mellitus were associated with the seroprevalence of HCV, whereas time spent as a CSW showed only borderline significance. Sexual activity was not an independent predictor of increased risk for HCV infection in female CSWs who had never been illicit IDUs.