Background:Many studies have been performed regarding the prevalence of hepatitis E in the general population, but there is controversial evidence for an increased risk of the infection in patients on maintenance hemodialysis (HD).Objectives:The primary end point of the present study was to determine if the prevalence of anti-hepatitis E virus IgG (anti-HEV IgG) is higher in patients on maintenance HD than in the normal population in Isfahan.Patients and Methods:In a case-control study performed in Isfahan in June 2012, we compared the seroprevalence of HEV among 274 patients on maintenance HD and 275 otherwise healthy individuals. The patients were recruited from 3 HD centers in Isfahan. Anti-HEV IgG was detected using a Dia Pro Diagnostic HEV enzyme immunoassay (ELISA) kit. Demographic and clinical data (sex, age, blood transfusion history, HD duration, age at HD initiation, and evidence of hepatitis B and hepatitis C infections) were obtained from the medical records of the HD patients.Results:Anti-HEV IgG was detected in 27 (9.9%) controls and 78 (28.3%) patients, with the difference being statistically significant (P < 0.05). Furthermore, there was a significant association between positive anti-HEV antibody, HD duration, and blood transfusion history in the HD patients.Conclusions:Considering the results, it seems necessary to conduct prospective studies in order to identify factors responsible for the high seroprevalence of HEV in Isfahan HD units.