Hepatitis E virus (HEV) is an emerging cause of acute hepatitis in Europe, particularly in southern France, and HEV is a new causative agent of chronic hepatitis and cirrhosis in immunocompromised patients. However, the data regarding HEV infection after kidney transplantation are still scarce with respect to the clinical issues that have been raised, and no study has specifically focused on kidney transplant recipients. This study described the clinical features and outcomes of HEV infections in a cohort of kidney transplant recipients living in southeastern France. The epidemiological, clinical, and virological characteristics of HEV infections diagnosed by PCR over a 53-month period were retrospectively analyzed in a cohort of 1,350 kidney transplant recipients monitored at the Marseille University Hospital. Sixteen HEV infections were diagnosed, all of which were autochthonous and involved genotype 3 viruses (HEV-3). Chronic infections occurred in 80% of these patients and resolved in half of the cases after a median time of 39 months. The rate of HEV clearance was 54% after a decrease in the dose of immunosuppressants. One patient developed liver cirrhosis 14 months after infection and experienced acute rejection after a decrease in the dose of immunosuppressants. Autochthonous HEV-3 infections in kidney transplant recipients progress to chronicity in most cases and might be complicated by early liver cirrhosis. Chronic HEV infection can resolve following the reduction of immunosuppressive therapy, but ribavirin may be required if reduction of the immunosuppressant dose is not associated with HEV clearance or is inappropriate for the patient management. J. Med. Virol. 85:462–471, 2013. © 2012 Wiley Periodicals, Inc.