Background: Hepatitis E virus (HEV) genotype 3 infections can have important clinical consequences. Objectives: To evaluate patients at risk and the effect of treatment strategies, we studied the clinical course and treatment outcome in patients diagnosed with HEV viremia in our hospital. Study design: Between January 2008 and March 2015 we included all patients with HEV genotype 3 (HEV-3) infections diagnosed by means of quantitative real-time reverse transcription-polymerase chain reaction test (RT-PCR). Clinical data were evaluated retrospectively. Results: In total 79 patients were included. Forty-nine patients (62%) were male, median age of all patients was 52 years (range 13-79). Sixty-one (77%) patients were immunocompromised. Three patients (3.8%) had only transient viremia, forty-three (54.5%) cleared the infection within six months and twenty-six (32.9%) developed chronic infection. Five patients (6.3%) were lost to follow-up. All patients developing chronic infection were immunocompromised. Overall, thirteen (16%) patients within this cohort died. Three patients had pre-existent liver diseases and died of liver-related causes. Time between diagnosis and death was shorter for patients with pre-existent liver diseases (p = 0.03). Twenty-eight percent of patients on immunosuppressive medication achieved viral clearance after reducing the dose of immunosuppressive therapy. Thirty patients (38.0%) were treated with off-label ribavirin in which 25 (83.3%) a sustained viral response has been documented. Conclusion: HEV genotype 3 viremia mainly presents in patients with underlying chronic liver diseases or an impaired immune system. Patients with pre-existent liver diseases are at high risk for complications and even death. The off-label use of ribavirin can cure HEV infection. (C) 2015 Elsevier B.V. All rights reserved.