BackgroundTo estimate the incidence of Hepatitis C virus (HCV) and the predictive factors through repeated routine laboratory analyses.MethodsAn observational cohort study was carried out in Quatre Camins Prison, Barcelona. The study included subjects with an initial negative HCV result and routine laboratory analyses containing HCV serology from 1992 to 2011. The incidence of infection was calculated for the study population and for sub-groups by 100 person-years of follow-up (100 py). The predictive factors were determined through Kaplan-Meier curves and a Cox regression. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated.ResultsA total of 2,377 prisoners were included with a median follow-up time of 1,540.9 days per patient. Among the total population, 117 HCV seroconversions were detected (incidence of 1.17/100 py). The incidence was higher between 1992 and 1995 (2.57/100 py), among cases with HIV co-infection (8.34/100 py) and among intravenous drug users (IDU) without methadone treatment (MT) during follow-up (6.66/100 py). The incidence rate of HCV seroconversion among cases with a history of IDU and current MT was 1.35/100 py, which is close to that of the total study population. The following variables had a positive predictive value for HCV infection: IDU (p<0.001; HR = 7,30; CI: 4.83–11.04), Spanish ethnicity (p = 0.009; HR = 2,03; CI: 1.93–3.44) and HIV infection (p = 0.015; HR = 1.97; CI: 1.14–3.39).ConclusionThe incidence of HCV infection among prisoners was higher during the first part of the study and among IDU during the entire study period. Preventative programs should be directed toward this sub-group of the prison population.