BACKGROUND:?Rapidplasmaregainpositiveand/ortreponema pallidum hemagglutination negative [RPR(+)/TPHA(-)] results were designated as biologic false-positive (BFP). There are limited data about BFP reactions against syphilis in patients with hepatitis C virus (HCV) infection. This study aimed to determine the prevalence of BFP reactions for syphilis in patients with HCV infection in a large sample and assess the relationship between BFP reactions and HCV infection. METHODS:? A total of 2656 patients with positive anti-HCV and 5600 healthy control subjects were enrolled in this study. Hepatitis C serology was determined by a second generation ELISA test for HCV antibody. Syphilis serology was determined by the RPR test. Those subjects with reactive RPR positive underwent the TPHA test. Demographics and laboratory data were collected by trained clinicians. RESULTS: Among 2656 patients, 111 (4.2%) had a reactive RPR test. Of the 111 patients who were subjected to reactive RPR test, 30 (27.0%) showed HCV(+)/RPR(+). Of 5600 healthy controls, 80 (1.4%) had a reactive RPR test. Fourteen (17.5%) controls with HCV(-)/RPR(+) had a non-reactive TPHA test. These represented 1.1% of all HCV-positive and 0.3% of all HCV-negative subjects (P0.05). CONCLUSIONS:?The data of this study demonstrate that HCV infection is associated with a false-positive RPR test. In this study BFPs were significantly more common in HCV positive patients compared to HCV-negative ones. Eosinophil abnormality can be considered as a predictor for BFP. Excessive BFPs must be considered in assessing the frequency of syphilis in a HCV-positive population and the importance of the treponemal specific serologic test should be emphasized for a diagnosis of syphilis in such population.