Field studies in large numbers of subjects unselected for risk factors are needed to assess the true prevalence and health burden of hepatitis C virus (HCV) infection. We assessed the prevalence, virological characteristics, risk factors and evidence of liver disease in a population of healthy subjects from an urban area of Sardinia. Hepatitis B virus (HBV) markers were also studied. The prevalence of antibodies to HCV (anti-HCV) (recombinant immunoblot assay [RIBA]-confirmed positive results) was 3.19% in 3324 workers and 7.11% in 225 elderly subjects, with a cumulative anti-HCV prevalence of 2.70% (95% CI 2.17–3.24). Males were more frequently positive than females (P < 0.01). The age-specific prevalence of HCV infection increased progressively in females. It showed two peaks in males: one in the fourth decade, the other in the seventh decade. HCV RNA was detected in 63.16% of the RIBA-positive sera, in 10% of the RIBA indeterminates and in none of the RIBA-negative specimens. Only 1.75% of anti-HCV-positive subjects had elevated transaminases. The frequency of HCV genotype 1b was 32.79%; of 1a, 21.31%; of 3a, 19.67%; of 4, 13.11%; and of 2a, 13.11%. HBV markers were found in 28.03% of workers. On multivariate analysis, male gender and tattooing were significantly associated with HCV and HBV infections: transfusion and travel with HCV, and age over 40 with HBV. The age prevalence rates of HCV infection in the Cagliari area reflect different risk factors that have been operative at different times. In this urban area, the large majority of HCV infections run a subclinical course.