BACKGROUND: Prison inmates are considered a high-risk population for blood-borne and enterically transmitted infections before and during their imprisonment. Hepatitis E virus (HEV) prevalence is unknown among French inmates, whereas a reassessment of human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalences is required to describe the epidemiologic evolution in this high-risk population. METHODS: A prospective survey was conducted from June to December 2017 in Fresnes prison, a penitentiary center with 2,581 inmates. In addition to HIV, HAV, HBV and HCV testing, which is offered to all patients at admission, we systematically offered HEV screening. Retrospective serological data for HIV, HBV and HCV, collected annually from 2014 to 2017, were also used to assess evolution. RESULTS: In 2017, 1,093 inmates were screened for HEV, HIV, HAV, HBV and HCV. Prevalences in this population were 8.2%, 1.3%, 62.7%, 1.9% and 2.9%, respectively. HEV seroprevalence increased with age (p<0.0001) and was higher among Eastern Europe born inmates (p<0.0001). Between 2014 and 2017, HIV seroprevalence remained steady, while a decrease in HBV and HCV seroprevalence was observed. CONCLUSIONS: Compared to the reported prevalence in French blood donors, HEV seroprevalence was remarkably low in French inmates. HIV, HAV, HBV and HCV prevalences among prisoners were higher than reported in the general population.