AimsLittle is known regarding acute heart failure (AHF) clinical characteristics and its hospital outcome in Latin America. This study sought to assess the prevalence of, and identify differences among, in‐hospital outcomes in patients hospitalized for AHF who were stratified by clinical phenotype at a hospital in Latin America.Methods and resultsThis is a retrospective cohort study of patients with AHF who were hospitalized in the coronary care unit of a Latin American teaching hospital from January 2006 to December 2018. Cox regression analysis was used to identify predictors of mortality. Of 21 042 patients admitted, 7759 (36.6%) had AHF. Their median age was 62 years, and 35% were women. De novo heart failure was seen in 39.4% of patients. Most common was AHF‐associated acute coronary syndromes (ACS‐HF) in 43.0%, decompensated heart failure (DHF) in 33.7%, hypertensive heart failure (HT‐HF) in 11.8%, and cardiogenic shock (CS) in 5.2%. Pulmonary oedema (PO) (3.3%) and right heart failure (RHF) (3.0%) were least frequent. Coronary artery disease was the most frequent aetiology in 56.5% of patients, valvular heart disease in 22.4%, and cardiomyopathies in 12.3%. Other less frequent aetiology included adult congenital heart disease (2.5%), lung diseases (2.1%), acute aortic syndromes (1.4%), pericardial diseases (0.8%), and intracardiac tumours (0.3%). Aetiology could not be established in 1.6% of patients. Before admission, patients with worsening chronic heart failure and reduced ejection fraction were treated with renin–angiotensin system blockers (60.4%), beta‐blockers (42.5%), or spironolactone (34.4%). The percentages of patients given in‐hospital management with intravenous diuretics, vasodilators, inotropes, and vasopressors were 81.2%, 33.4%, 18.9%, and 20.4%, respectively. The overall in‐hospital mortality was 17.9% (71.3%, 43.9%, 23.8%, 14.9%, 13.6%, and 10.1% for CS, PO, RHF, DHF, ACS‐HF, and HT‐HF, respectively; P < 0.0001). Multivariate analysis revealed that PO (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.73–4.14, P < 0.0001) and CS (HR 3.37, 95% CI 2.12–5.35, P < 0.0001) were independent predictors of in‐hospital mortality. Use of intravenous diuretics was linked to reduction of in‐hospital mortality (HR 0.70, 95% CI 0.59–0.59, P < 0.0001). By contrast, increased in‐hospital mortality was associated with the use of intravenous inotrope or vasopressor (HR 1.49, 95% CI 1.27–1.76 and HR 2.91, 95% CI 2.41–3.51, P < 0.0001, respectively).ConclusionsReal‐world evidence from a university hospital in Latin America shows that the high mortality among patients with AHF may depend, among other factors, on patients' AHF clinical phenotypes. The clinical characteristics and aetiologies of AHF appear to differ between these data from Mexico and those from European and US registries.