We identified risk factors for Buruli ulcer (BU) in Benin in an unmatched case-control study at the Centre Sanitaire et Nutritionnel Gbemoten in southern Benin. A total of 2,399 persons admitted from 1997 through 2003 and 1,444 unmatched patients with other conditions in 2002 were recruited. Adjusted odds ratios were determined for age, sex, place of residence, Mycobacterium bovis BCG vaccination at birth, type of water for domestic use, and occupation. Children <15 years of age and adults >49 years of age had a higher risk for BU. Use of unprotected water from swamps was associated with increased risk for BU; this association was strongest in adults >49 years of age. Sex was not a risk factor for BU. Our data showed that BU was mainly associated with age, place of residence, and water sources in all age groups. Risk for BU was higher in BCG-vaccinated patients >5 years of age.