In France, since 2006, the number of confirmed cases of locally acquired hepatitis E (HE) has increased significantly. In 2010, a descriptive study of locally acquired HE cases was conducted to generate hypotheses regarding modes of infection and sources of transmission. Cases of locally acquired HE confirmed by the National Reference Center (CNR) were interviewed about their exposures in the 2 to 10 weeks prior to the onset of illness. Clinical, laboratory, and epidemiological data were collected for 139 indigenous cases. Sixty-five percent of them resided in southern France, 59% reported having an underlying medical condition, and 74% were infected with genotype 3f. Consumption of raw pork liver products during the incubation period was more common among cases residing in southern France (47%) than among those residing in the north (25%). HE is a common infection, more frequently diagnosed in southern regions where cases more often report consumption of raw pork liver products. A case-control study could determine the proportion of HE cases attributable to the consumption of such products as well as to other risk factors.