Introduction: Chagas disease is an important cause of stroke in Latin America that results in major long-term disability. Ischemic cerebrovascular events (ICE) can occur at any stage of the disease and may be useful in predicting clinical outcomes.Hypothesis: ICE are additional risk factors for mortality in Chagas disease patients.Methods: This study prospectively enrolled 360 patients with Chagas cardiomyopathy from 1999 to 2016. The primary outcome was cardiac death, and non-cardiovascular deaths or cardiac transplantation were censored. ICE during the follow-up, exposure variable, was time-dependent adjusted in proportional hazards model. Missing data were treated by multiple imputations.Results: The mean age was 49.6 ±12 years, with 215 male (60%). At baseline, 266 patients (74%) were in NYHA functional class I or II with left ventricular ejection fraction (LVEF) of 37 ± 12%. Stroke before enrollment into the study was diagnosed in 32 patients (9%), atrial fibrillation in 30 patients (8%), and 103 (29%) were on anticoagulant therapy. Apical aneurysms were detected in 143 patients (40%), whereas LV mural thrombi were found in 56 patients (15.5%). During a mean follow-up of 4 years (range 0.3 -15.8), 60 patients had suffered ICE (44 stroke, and 16 transient ischemic attack), and 131 patients had died, mainly due to heart failure. Of the 44 patients with stroke, 7 were recurrent stroke, and 37 experienced a first stroke. Nineteen patients underwent cardiac transplantation, and 5 died from non-cardiovascular causes, and they were censored from the analysis. After adjustment for well-established predictors of death in Chagas disease, including NYHA functional class, LVEF, right ventricular function, E/eʼ ratio, and left atrial volume, ICE during the course of follow-up, analyzed as time-dependent variable, were predictors of death (adjusted HR 2.13, 95% CI 1.29-3.53; p=0.003).Conclusions: ICE are strong predictors of cardiac death in patients with Chagas disease, independent of other prognostic markers in this population. The long term risk of death is 2.1 times higher in patients with ICE than in those without events.