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Background: Chagas disease is one of the most common diseases in Latin‐America, and cardiac involvement is a significant cause of death. Assessment of myocardial strain may detect early myocardial damage. Objectives: To determine differences in longitudinal strain using speckle tracking to assess regional and global left ventricular function in patients with the indeterminate form of Chagas disease, in comparison with a control group. Methods: This is a retrospective matched case–control study, conducted in a single center. We evaluated 45 adult patients with Chagas disease, diagnosed with 2 serological methods, without evidence of cardiac involvement, who were compared with 45 healthy control subjects, who were sex‐ and age‐matched. All patients underwent Doppler echocardiography and longitudinal strain with speckle tracking. Results: Median age was 59 years, and 60% were female. Echocardiographic parameters were similar in patients with Chagas and control subjects. In patients with Chagas, global strain differed significantly from that of control subjects (−17 vs −20.3, P <.001). Segmental strain showed 7 abnormal segments in patients with Chagas (P <.05). Conclusions: In patients with the indeterminate form of Chagas disease, global and segmental longitudinal peak systolic strain is reduced compared with healthy subjects, thus suggesting that it could be a sensitive technique to detect early myocardial damage. These findings could provide useful information regarding the pathophysiology of cardiac involvement and understand whether they might have prognostic usefulness or help develop strategies to modify the course and prognosis of patients with Chagas disease. A longitudinal prospective study would be necessary to validate our findings. [ABSTRACT FROM AUTHOR]