Background Infection by hepatitis E virus (HEV) can cause a high burden of morbidity and mortality in countries with poor access to clean water and sanitation. Our study aimed to investigate the situation of HEV infections in the Central African Republic (CAR). Methods A retrospective analysis of the blood samples and notification forms collected through the national yellow fever (YF) surveillance program, but for which a diagnosis of YF was discarded, was carried out using an anti-HEV IgM ELISA and a HEV-specific RT-PCR. Results Of 2883 YF-negative samples collected between January 2008 and December 2012, 745 (~ 26%) tested positive by at least either of the 2 tests used to confirm HEV cases. The results revealed that the CAR was hit by a large HEV outbreak in 2008 and 2009. The results also showed a clear seasonal pattern with correlation between HEV incidence and rainfall in Bangui. A phylogenetic analysis showed that the circulating strains belonged to genotypes 1e and 2b. Conclusions Overall, this study provides further evidences that HEV can be a significant cause of acute febrile jaundice, particularly among adults during rainy season or flood, in a country from Sub-Saharan Africa.