The object of this study was to investigate the prevalence of Hepatitis C virus (HCV) by second-generation testing and to determine the effectiveness of risk factor-guided screening. We performed a prospective study of HCV exposure determined by second-generation enzyme-linked immunoadsorbent assay (ELISA) and confirmed by radioimmunoblot assay (RIBA). Risk factors (RF) were interpreted by univariate and multivariate analyses. Eight hundred eighty-six consecutive patients were tested for HCV over a 1-year period; 34 women tested positive for HCV and 32 were confirmed by RIBA (prevalence 3.6%). Forty-nine percent of women had at least one RF. Age, intravenous drug use, history of hepatitis strongly correlated with HCV (p <0.001). RF screening had a sensitivity of 81%. Twenty-one percent of women with HCV had no RF. The absence of any RF had a negative predictive value of 98.7%. RF screening is effective in identifying patients at low risk for HCV.