BACKGROUND: Mycobacterium leprae infection has recently been detected in wild armadillos in Brazil. Leprosy is still endemic in Brazil and although its transmission is mostly by person-to-person contact, many cases report no history of previously known leprosy contact. It has been suggested that other sources of M. leprae may contribute to the transmission of leprosy in some areas. AIM: Our objective was to investigate whether contact with armadillos is associated with leprosy. METHODS: A case-control study was carried out in Brazil. Data was collected from 506 leprosy patients and 594 controls on exposure to armadillos and age, sex, place of birth and living conditions. Univariate analysis and unconditional logistic regression were conducted to investigate whether leprosy was associated with exposure to armadillos. RESULTS: Direct armadillo exposure was reported by 68% of leprosy cases and by 48% of controls (P < 0.001) roughly doubling the risk of leprosy, with odds ratio (OR) 2.0, 95% confidence interval (CI) [1.36-2.99]. CONCLUSION: The results of this study suggest that direct exposure to armadillos is a risk factor for leprosy in Brazil.