AbstractA fraction of plasma donations undergoes hepatitis E virus (HEV) RNA screening since late 2014 in France. The aim of this study was to determine the frequency of HEV RNA as well as the viral load and the evolution of genotype distribution over a 3‐year period (2015‐2017) in asymptomatic blood donors in comparison with symptomatic patients routinely diagnosed. The overall detection rate of HEV RNA in plasma donations was 0.10% during the 3‐year period, with a median viral load of 717 IU/mL (range: <60‐168 000 IU/mL) in the 189 samples found HEV RNA positive. One hundred and twenty samples (64.4%) were successfully HEV genotyped. Most strains were HEV3f (n = 54; 44.3%) and HEV3c (n = 46; 37.7%). The genotype distribution was not different throughout the 3‐year period and we found no association between the genotype and where the blood donors lived (P = 0.96). The HEV genotype distributions in infected blood donors and symptomatic patients were similar. However, the symptomatic patients had a higher viral load (median 282 000 IU/mL; range: <60‐136 000 000 IU/mL; P < 0.01) than the blood donors. Overall, asymptomatic blood donors and patients with symptomatic hepatitis E had similar genotype distributions but the blood donors had lower viral loads.