Aims This study aimed to analyse the clinical presentation and prognosis of patients with Chagas cardiomyopathy and decompensated heart failure (HF), as compared with other aetiologies. Methods and results A prospective cohort of patients admitted with decompensated HF. We included 767 patients (63.9% male), with median age of 58 years [interquartile range 48.2-66.7 years]. Main aetiologies were non-Chagas/non-ischaemic cardiomyopathies in 389 (50.7%) patients, ischaemic disease in 209 (27.2%), and Chagas disease in 169 (22%). Median left ventricular ejection fraction was 26% (interquartile range 22-35%). Patients with Chagas differed from both patients with non-Chagas/non-ischaemic and ischaemic cardiomyopathies for a higher proportion of cardiogenic shock at admission (17.8%, 11.6%, and 11%, respectively, P < 0.001) and had lower blood pressure at admission (systolic blood pressure 90 [80-102.5], 100 [85-110], and 100 [88.2-120] mmHg, P < 0.001) and lower heart rate (heart rate 71 [60-80], 87 [70-102], and 79 [64-96.5] b.p.m., P < 0.001). Further, patients with Chagas had higher serum BNP level (1544 [734-3148], 1061 [465-239], and 927 [369-1455] pg/mL, P < 0.001), higher serum bilirubin (1.4 [0.922.44], 1.2 [0.77-2.19], and 0.84 [0.49-1.45] mg/dL, P < 0.001), larger left ventricular diameter (68 [63-73], 67 [58-74], and 62 [56.8-68.3] mm, respectively, P < 0.001), lower left ventricular ejection fraction (25 [21-30]%, 26 [22-35]%, and 30 [25-38]%, P < 0.001), and a higher proportion of patients with right ventricular function (48.8%, 40.7%, and 25.9%, P < 0.001). Patients with Chagas disease were more likely to receive inotropes than patients with non-Chagas/non-ischaemic and ischaemic cardiomyopathies (77.5%, 67.5%, and 62.5%, respectively, P = 0.007) and also to receive intra-aortic balloon pumping (30.8%, 16.2%, and 10.5%, P < 0.001). Overall, the rates of death or urgent transplant were higher among patients with Chagas than in other aetiologies, a difference that was driven mostly due to increased rate of heart transplant during hospital admission (20.2%, 10.3%, and 8.1%). The prognosis of patients at 180 days after hospital admission was worse for patients with Chagas disease as compared with other aetiologies. In patients with Chagas, age [odds ratio (OR) = 0.934, confidence interval (CI)(95%) 0.901-0.982, P = 0.005], right ventricular dysfunction by echocardiography (OR = 2.68, CI95% 1.055-6.81, P = 0.016), and urea (OR = 1.009, CI95% 1.001-1.018, P = 0.038) were significantly associated with prognosis. Conclusions Patients with Chagas cardiomyopathy and decompensated HF have a distinct clinical presentation and worse prognosis compared with other aetiologies.