The aim of this study was to evaluate the persistence and protective role of antibodies to hepatitis E virus (anti-HEV) after natural hepatitis E infection. A retrospective analysis of immunoglobulin G (IgG) anti-HEV was performed in 37 patients followed-up for 5 years after epidemics of HEV. Two patients with sporadic hepatitis E (HE) were followed-up for 12 and 8 years. All patients infected during epidemics of HE were positive for IgG anti-HEV at 5 years of follow-up (geometric mean titre: 174.75). The two patients with sporadic HE were positive for IgG anti-HEV at the end of 12 and 8 years of follow-up (the IgG anti-HEV titre was 1: 200 in each patient). This study showed protection against disease by antibodies to HEV. It was therefore concluded that hepatitis E may be preventable by an efficacious vaccine.