Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It can result in permanent physical disabilities if not diagnosed early. A case-control study was conducted to identify the factors associated with the occurrence of leprosy in individuals living in a region of high incidence of the disease in the Tocantins state in northern Brazil. Sixty cases were diagnosed between 2016 and 2018, and 120 controls were included in the study. The control group consisted of residents from the same area as the cases, the same sex, and with an age variation of up to 5 years. Data were collected through interviews with each participant. Associations were assessed by univariate analysis, followed by logistic regression analysis. The following factors were associated with leprosy in the logistic regression model: households with no more than four rooms (OR = 4.01), absence of a BCG vaccination scar (OR = 2.16), and a previous case of leprosy in the family (OR = 4.32). The data indicated that a close relationship between individuals of the same family in small households, without any immunological protection, and with a history of leprosy cases, significantly increased the risk of M. leprae infection and development of leprosy.