ABSTRACT Chagas disease (CD) is a neglected tropical disease associated with poverty in which patients are surrounded by stigma. These factors can contribute to reducing health-related quality of life (HRQoL). Therefore, a broad discussion of HRQoL in the CD population is required. This study aimed to discuss the main findings of HRQoL in patients with CD, focusing on the association between sociodemographic and lifestyle factors, echocardiographic and functional determinants, and the effect of non-invasive interventions on HRQoL. A literature search of the MEDLINE, Web of Science, CINAHL, Scopus, and LILACS databases was performed with no data or language restrictions. Twenty-two articles were included in this meta-analysis. In general, HRQoL is worse in patients with CD than in healthy individuals, particularly in the presence of cardiovascular and/or gastrointestinal symptoms. Sex, age, functional class, level of physical activity, healthy habits, and medications received could affect HRQoL. Among the echocardiographic and functional determinants, decreased systolic function seems to negatively affect HRQoL. No association with the peak oxygen uptake was observed in the maximal tests. By contrast, well-tolerated field tests with submaximal intensities were associated with HRQoL. Both pharmaceutical care and exercise training have a positive effect on the HRQoL of patients with Chagas cardiomyopathy, and the mental component can be a prognostic marker in this population. In conclusion, assessment of HRQoL can provide important information about the health status of patients with CD, and its use in clinical practice is warranted.