Most cases of hepatitis E viral (HEV) infection in developed countries are autochthonous. Nevertheless, the reported seroprevalence of HEV varies greatly depending on the geographical area and the performance of the immunoassay used. We used validated assays to determine the prevalence of anti-HEV immunoglobulin G (IgG) and IgM among 10,569 French blood donors living in mainland France and three overseas areas. Epidemiological information was collected using a specific questionnaire. We found an overall IgG seroprevalence of 22.4% (8%-86.4%) depending on the geographical area (P < 0.001). The presence of anti-HEV IgG was associated with increasing age (P < 0.001) and eating pork meat (P 5 0.03), pork liver sausages (P < 0.001), game meat (P < 0.01), offal (P < 0.001), and oysters (P 5 0.02). Conversely, drinking bottled water was associated with a lower rate of anti-HEV IgG (P 5 0.02). Overall IgM seroprevalence was 1% (0%-4.6%). The frequency of anti-HEV IgM was higher in donors living in a high anti-HEV IgG seroprevalence area (1.9% versus 0.7%, P < 0.001) and in those eating pork liver sausage (1.4% versus 0.7%, P < 0.01), pât e (1% versus 0.4, P 5 0.04), and wild boar (1.3% versus 0.7%, P < 0.01). Conclusion: HEV is endemic in France and hyperendemic in some areas; eating habits alone cannot totally explain the exposure to HEV, and contaminated water could contribute to the epidemiology of HEV infection in France. (HEPATOLOGY 2016;63:1145-1154 H epatitis E virus (HEV) is a single-stranded, positive sense RNA virus that is a member of the Hepeviridae family.(1) Four major genotypes of human HEV are recognized. HEV genotypes 1 and 2 have been found only in humans and are prevalent in developing countries. They are responsible for both sporadic cases and large outbreaks linked to drinking contaminated water. HEV genotypes 3 and 4 are anthropozoonotic and prevalent in developed countries. These HEV genotypes have been detected in a wide range of domestic and wild animals, which are believed to play a major role in the human epidemiology of the virus. (2) HEV genotypes 1 and 2 mainly affect young adults, mostly men, aged 15-30. Almost half of all cases become jaundiced, and pregnant women during the third trimester and patients with underlying chronic liver disease are most at risk of a severe form of hepatitis E.(3) HEV genotypes 3 and 4 mainly affect older men. Most infections are asymptomatic, but patients suffering from chronic liver disease are at risk of developing acute liver failure.(3) Immunosuppressed individuals infected with genotype 3 or 4 may develop a chronic infection that can rapidly progress to cirrhosis. (4) Autochthonous infections are frequently reported in developed countries, particularly in western Europe. (5) The virus can be transmitted by contaminated food, (3) mainly undercooked pig meat, (6) although other modes of contamination have been described. They are often occupational, such as direct exposure to animals or to slaughterhouse meat. The risk of HEV transmission through blood pro...