Chagas cardiomyopathy and ischemic heart disease (IHD) are frequent causes of chronic systolic heart failure (CHF) in areas where the former is endemic. Nonetheless, a specific comparison of outcome and role of etiology of CHF failure has not been performed in patients with both conditions.Two-hundred twenty two patients with Chagas cardiomyopathy and 79 with IHD with CHF were included in the study. A Cox proportional hazards model was used to establish independent predictors of mortality for the studied population. Survival analysis was performed with the Kaplan-Meir product limit method.In the multivariable model, Beta-Blocker therapy [(hazard ratio (HR)=0.36; 95% confidence interval (CI) 0.24 to 0.52; p<0.005)], Chagas etiology of CHF (HR=3.6; 95% CI 2.0 to 6.5; p<0.005), serum sodium levels (HR=0.95; 95% CI 0.91 to 0.98; p<0.005), digoxin use (HR=2.1; 95% CI 1.19 to 3.80, p=0.01), and spironolactone use (HR=1.7; 95% CI 1.10 to 2.80; p=0.02) were determined independent predictors of all-cause mortality for this cohort. Probability of survival at 12, 24, 36, 48, and 60 months was 92%, 92%, 88%, 81%, and 78%, respectively, in IHD patients, and 79%, 61%, 49%, 41%, and 35%, respectively, in Chagas cardiomyopathy patients (p<0.005).Outcome in patients with chronic systolic heart failure secondary to Chagas cardiomyopathy is poorer than that seen in those with IHD.