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Summary: In Europe, autochthonous hepatitis E virus (HEV) infection is mainly a foodborne zoonosis, but it is also transmitted by blood transfusion. Despite the numerous prevalence surveys, only a few studies have investigated HEV incidence. We aimed to determine HEV incidence and risk factors among blood donors in a hyperendemic area in Central Italy. Of 296 blood donors who had tested HEV negative in two previous seroprevalence surveys in L'Aquila, 198 agreed to undergo at least another blood sampling for estimating HEV incidence nearly 2 years after the prevalence surveys. Ten newly acquired infections were detected, yielding an overall incidence of 2.1/100 person‐years (95%CI: 1.0‐3.9), with an estimated participant's cumulative probability of becoming HEV infected of 6.5% (95%CI: 3.5‐12.0) at 4 years after enrolment. Seven newly infected blood donors were IgG positive only, two were IgM positive (one also IgG positive) and one was HEV RNA positive only, harbouring subtype 3c. Incident infection was most strongly associated with eating game meat, raw‐dried pork liver sausage and raw‐dried wild boar sausage. None of these exposures was statistically significant, even if eating raw‐dried wild boar sausage approached significance (P = 0.06). The HEV incidence we found was considerable compared with other similar studies. The nearly significant association of incident infection with wild boar and other game meat consumption was in agreement with the 3c subtype isolation in the viremic donor. However, beyond eating habits, also other exposure sources are likely important in hyperendemic areas, where incidence and risk exposure studies need to be undertaken for effectively preventing HEV transmission. [ABSTRACT FROM AUTHOR]