Background and Objectives:A global distribution has been shown for hepatitis E virus (HEV) infection. Although the fecal-oral was considered as the primary infection route, there is controversial evidence for increased risk of the infection and consequent problems in patients on maintenance hemodialysis (HD) with suppressed immunity. The aim is to find if the prevalence of anti-HEV IgG, in patients with maintenance HD is higher than normal population in southwest of Iran.Materials and Methods:During November and December 2010, in a cross-sectional study we compared the seroprevalence of HEV among 80 patients with maintenance HD and 276 healthy individuals from Jahrom and Shiraz, Southwest of Iran. In addition to the clinical and laboratory records, serum samples were tested for the presence of IgG anti-HEV antibody by enzyme immunoassay (ELISA) test. The Chi-square, the Student's ‘t’ and Fisher's exact tests were used for the statistical analysis.Results:ELISA tests detected anti-HEV antibody in five males of the patients (6.3%) and in eight of the healthy controls (2.9%, 6 males and 2 female) which statistically were not different. The mean levels of the aspartate aminotransferase and the alanine aminotransferase in the sera of the patients were 19.96±11.08U/L and 23.93±14.26 IU/L, respectively. However, no one of the individuals with positive anti-HEV antibody showed elevated liver enzymes. Moreover, there was not a significant association between positive anti-HEV antibody result, age and the history of the hemodialysis.Conclusions:We did not observe statistically significant higher anti-HEV prevalence among patients with chronic HD; however, more safety precaution is needed to keep HD patients from the risk of possible exposure to HEV infection.