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The aim was to estimate seroprevalence and prevalence of hepatitis C virus (HCV) infection in a small health area of the Valencian Community, Spain.This is a descriptive cross-sectional study aimed at estimation of HCV infection prevalence in the whole adult population (25–70 years old), that is, a pilot study for an eventual population-based screening program.A total of 5849 participants aged 25–70 years (51% male) were invited to participate by regular mail. Overall, 143 letters were returned owing to errors in the addresses. Of 5706 participants, 2637 (46.2%) participated in the study. Rapid test of anti-HCV antibody detection was positive in 30 cases (HCV seroprevalence 1.14%, 95% confidence intervals: 0.73–1.55%). Of those, seven were not aware of their condition. Participants who had a positive result in the rapid test of anti-HCV detection were given a confirmatory test by enzyme immune assay, and all had a positive result. RNA-HCV determination by quantitative PCR in positive anti-HCV patients showed positive viremia in 13 (43.3%) cases, of which five were not aware of the disease. Of the 17 patients who had negative viremia, two were unaware of their HCV status, one was a carrier of anti-HCV and was already aware of his condition, and 14 had been previously treated with satisfactory results. Regarding fibrosis, of the seven patients who were unaware of HCV infection, none of them had significant fibrosis. Moreover, 26 (86.7%) anti-HCV positive patients were reported to have one or more risk factors for HCV infection.HCV screening strategies applied to the general population are good means to diagnose and treat patients who are not aware of their infection, avoiding new transmissions as well as disease progression.