The goals of this cross-sectional study conducted in the Zè district of Benin were to determine the overall distribution and prevalence of Buruli ulcer (BU) and to identify environmental and behavioral risk factors. A total of 425 current or previous BU patients from the study district were included. Data was obtained by direct observation, semi-structured interviews, and document review. The main findings can be summarized as follows. The overall prevalence of BU in the Zè district in 2006 was 52 cases per 10000 inhabitants. The prevalence of current and previous cases was 28.1 and 23.9 per 10 000 inhabitants respectively. The distribution of BU within the district was highly variable from one subdistrict to another and from one village to another within the same subdistrict. The subdistricts showing the highest and lowest endemicity were Djigbé with 265 cases per 10 000 inhabitants and Koundokpoé with 3 cases per 10 000 inhabitants respectively. Proximity of the hamlets to water bodies was a risk factor for the disease.