The incidence of hepatitis A is falling. In contrast, autochthonous hepatitis E is an emerging infection in developed countries. The objective of this study was to compare both laboratory-confirmed cases of hepatitis A and autochthonous hepatitis E over a 2-year period in Cornwall and Devon and anti-hepatitis A virus (HAV) IgG and anti-hepatitis E virus (HEV) IgG seroprevalence in blood donors. The databases of microbiology laboratories in Cornwall and Devon were searched for the number of diagnostic HEV and HAV assays performed during 2005-2006 and the number of confirmed cases of acute hepatitis A and hepatitis E detected. Patients were followed up until recovery or death. Sera from 500 blood donors from the regional centre were tested for HEV and HAV IgG. In total, 28 cases of autochthonous hepatitis E were identified from 838 assays, and 20 cases of hepatitis A were identified from 4503 assays. Compared to hepatitis A cases, patients with hepatitis E were older (mean age 61 vs. 45 years, P = 0.003), less likely to present in winter (P = 0.028) and had more complications (five vs. one). The IgG seroprevalence rates in blood donors were 45% for HAV and 16% for HEV. There was no relationship between HAV and HEV IgG seropositivity. Autochthonous hepatitis E may be more common than hepatitis A, affects older patients, is less likely to occur in winter and may be associated with more complications. Patients with acute hepatitis, whatever their age or travel history, should be tested for HEV.