Acute heart failure (AHF) is a common etiology of hospitalization and is associated with morbidity, including bleeding. In this study, the authors sought to assess the incidence, types, and associates of major bleeding in patients hospitalized with AHF. The National Inpatient Sample from October 2015 to December 2018 was used to identify patients with AHF. The incidence of common bleeding etiologies, and patient demographics, co-morbidities, associated acute cardiac diagnoses, and invasive procedures, were identified. The multivariable logistic regression was used to identify predictors of bleeding and the association of bleeding episodes with inpatient mortality. During the study period, 1,106,634 patients were admitted with a primary diagnosis of AHF, of whom 58,955 (5.3%) had an episode of bleeding. Common bleeding sources were gastrointestinal (25.7%), hematuria (24%), respiratory (23.6%), and procedure-related bleeding (2.5%). Major bleeding was more common in patients with AHF with preserved ejection fraction (odds ratio 1.14, confidence interval 1.12 to 1.16, p <0.001) versus AHF with reduced ejection fraction and in men (odds ratio 1.3, confidence interval 1.29 to 1.31, p <0.001). Major bleeding was associated with higher mortality (7.0% vs 2.4%, p <0.001), longer length of stay (7 vs 4 days, p <0.001), and higher inpatient costs ($49,658 vs $27,636, p <0.001). In conclusion, major bleeding occurs in 5.3% of patients hospitalized with AHF and is associated with higher inpatient mortality and costs and longer length of stay.