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Chagas disease (CD) is a neglected tropical disease and its main consequence is chronic chagasic cardiomyopathy (CCC). The clinical manifestations of CD can cause functional limitation and impact on the perception of quality of life (QoL). We evaluated the QoL profile of patients with CD living in remote regions, and their association with socio-demographic, behavioral, and clinical characteristics.A cross-sectional study, using the baseline of a cohort study (SaMi-Trop) was conducted in the state of Minas Gerais, Brazil, an endemic region for CD. The cohort is composed of 1959 patients with CD. The patients were interviewed, and blood collection and electrocardiogram (ECG) were performed. The WHOQOL-BREF scale was used to assess QoL. Descriptive statistics were performed and, for the QoL scale, measures of central tendency and dispersion were calculated. Inflated beta regression models constructed using the gamlss framework were used, and fitted using R software. A significance level of 5% for all analyzes was adopted.QoL was evaluated in 625 participants. The Environment (57.66) and Social Relationships (73.17) domains presented the lowest and highest QoL score respectively. There was no statistically significant difference between QoL domains in the presence of CCC. In the multivariate analysis, the factors associated with a lower QoL were in the Physical domain age increase (OR: 0.95, CI: 0.91–0.99) and using an angiotensin converting enzyme inhibitor (OR 0.89; CI: 0.80–0.99); in the Social Relations domain a history of acute myocardial infarction (OR: 0.75; CI: 0.61–0.92); and in the Environment domain age increase (OR 0.94, CI 0.91–0.97). The factor associated with higher QoL was the use of angiotensin receptor blockers (OR: 1.15; CI 1.04–1.26).The findings of this study reinforce the importance of QoL indicators for planning care and clinical management of patients from remote regions with CD. Trial registration: NCT02646943. Author summary: Chagas disease (ChD) is a neglected tropical disease, with the majority of the individuals affected living in Latin America. Functional limitation and poor perception of quality of life (QoL) may be identified. QoL indicators are important for planning and to improve patients care. However there is a gap in the literature regarding the evaluation of QoL in patients living with chronic CD, in remote regions assisted by primary health care in their territory of residence. A cross-sectional study was conducted using the baseline of a prospective cohort performed in remote towns in Minas Gerais state, Brazil. Lower QoL scores were identified in the Environment domain followed by the Physical domain. Higher scores were found in the Social Relations domain. Low QoL scores have been associated with clinical aspects such as use of angiotensin converting enzyme inhibitor (ACEI), and history of acute myocardial infarction, and socio-demographic aspects such as increasing age. QoL is positively associated with medicine use of angiotensin receptor antagonists (ARA). The subjective perception of QoL was not associated with the severity of the disease using as a marker the presence of CCC in the evaluated population. [ABSTRACT FROM AUTHOR]