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Objective: Congenital toxoplasmosis is a public health problem in Brazil. This study aimed to determine risk factors associated with congenital toxoplasmosis in Minas Gerais which is the second largest Brazilian State based on number of inhabitants, and its territorial extension is larger than that of France., Methods: Population-based case-control study to assess the association between congenital toxoplasmosis and maternal exposure to infection risk factors. The study included mothers/children participating in the Minas Gerais Newborn Screening Program. The cases consisted of 175 mothers of infected children, and the controls consisted of 278 mothers of children without suspected infection. The associations were assessed through binomial logistic regression with p ≤ 0.05., Results: The variables associated with lower probability of toxoplasmosis were: older mother age (OR = 0.89; CI95%  = 0.85-0.93), higher level of education (OR = 0.85; CI95% = 0.78-0.92), access to potable water (OR = 0.21; CI95% = 0.08-0.51), and home with flush toilet (OR = 0.18; CI95% = 0.04-078). The variables associated with higher probability of infection were: cats in the neighborhood (OR = 2.27; CI95%  = 1.27-4.06), owning or visiting homes with domestic cats (OR = 1.90; CI95%  = 1.09-3.31), handling the soil (OR = 2.29; CI95%  = 1.32-3.96), and eating fresh meat not previously frozen (OR = 3.97; CI95%  = 2.17-7.25). After stratification according region of residence (rural or urban/peri-urban), home with flush toilet and consumption of treated water were protective against the disease only in the rural stratum., Conclusions: In Minas Gerais, congenital toxoplasmosis has been associated with poor socioeconomic conditions. Considering maternal exposure to sources of Toxoplasma gondii, the predominating risk factors were those related to the ingestion of oocysts. It is expected that these results will contribute to development of a program for prevention of congenital toxoplasmosis adapted to the reality of the population of Minas Gerais. The differences between populations living in rural and urban areas regarding the main risk factors for toxoplasmosis point to the need of considering regional specificities in planning strategies to control congenital toxoplasmosis.