Objective - To characterize cases of hepatitis E in France from 2006 to 2008 by comparing clinical and epidemiological data with those from 2002 to 2004. Method - Based on cases of hepatitis E diagnosed in France by laboratories testing for serological and molecular markers, case investigations (clinical data, HEV exposure factors) were conducted with clinicians using the exploratory hepatitis E questionnaire available online on the National Reference Center’s website: http://www.cnr.vha-vhe.aphp.fr. Results - From 2006 to 2008, 264 cases of locally acquired hepatitis E, 51 cases of imported hepatitis E, and 54 cases of hepatitis E with an unspecified epidemiological context were reported, predominantly among men over 55 years of age for locally acquired cases, with a geographic distribution following a north-south gradient. Among the documented indigenous cases, hepatitis E occurred in 5% of immunocompromised patients, with viremia detected for two to 15 months. Exposure to the animal reservoir (through consumption of undercooked pork, or via occupational or recreational activities) was the most frequently cited risk factor (35–40% of investigated cases), regardless of the region where the case was identified. In 36% of cases, no risk factor could be identified due to lack of data or investigation conducted too late. Conclusion - To improve the investigation of locally acquired cases, enhanced surveillance for hepatitis E was implemented by health authorities in 2009, based on the voluntary participation of physicians and laboratories performing diagnostic testing. (R.A.)