Hepatitis E virus (HEV) is largely confined to travelers returning from endemic areas, but the number of autochthonous cases of acute HEV infections in developed countries is increasing. Reservoirs for HEV are surface water, wild boar meat, and raw or undercooked pork meat. Usually, hepatitis E is a self-limiting disease presenting with acute hepatitis as a major clinical symptom. The seroprevalence of anti-HEV-IgG was investigated in 833 serum samples routinely collected from patients admitted to the university hospital in Frankfurt a. M., Germany (FFM) between 01.06.2008 and 31.12.2010. After determination of overall seroprevalence, we tested serum samples from patients diagnosed with acute elevation of liver enzymes (AELE), psychiatric (PSYCH), infectiological patients and serum samples from the red-cross blood donor service in FFM for anti-HEV-IgG using an ELISA. Between 01.06.2008 and 31.12.2010, 833 serum samples were analyzed for anti-HEV-IgG using an ELISA. We observed an overall seroprevalence of anti-HEV-IgG of 11.2% (95%CI: 9.6-13.2). Significantly higher rate of seropositivity was found in the group of PSYCH (26.0%; 95%CI: 14.63-40.34) and AELE (30.0%; 95%CI: 17.86-44.61). Overall seroprevalence of anti-HEV-IgG in FFM is higher than in Germany on average. The group of AELE and PSYCH shows significantly more often marker of HEV infections than other groups in our collective.