ABSTRACT: Background Heart failure (HF) imparts a significant clinical and economic burden on the health system in the United States. Methods and Results We used the National Inpatient Sample database between September 2002 and December 2016. We examined trends of comorbidities, inpatient mortality, and healthcare resource use in patients admitted with acute HF. Outcomes were adjusted for demographic variables, comorbidities, and inflation. A total of 11 806 679 cases of acute HF hospitalization were identified. The burden of coronary artery disease, peripheral vascular disease, valvular heart disease, diabetes mellitus, hypertension, anemia, cancer, depression, and chronic kidney disease among patients admitted with acute HF increased over time. The adjusted mortality decreased from 6.8% in 2002 to 4.9% in 2016 (P-trend<0.001; average annual decline, 1.99%), which was consistent across age, sex, and race. The adjusted mean length of stay decreased from 8.6 to 6.5 days (P<0.001), but discharge disposition to a long-term care facility increased from 20.8% to 25.6% (P<0.001). The adjusted mean cost of stay increased from $51 548 to $72 075 (P<0.001; average annual increase, 2.78%), which was partially explained by the higher proportion of procedures (echocardiogram, right heart catheterization, use of ventricular assist devices, coronary artery bypass grafting) and the higher incidence of HF complications (cardiogenic shock, respiratory failure, ventilator, and renal failure requiring dialysis). Conclusions This national data set showed that despite increasing medical complexities, there was significant reduction in inpatient mortality and length of stay. However, these measures were counterbalanced by a higher proportion of discharge disposition to long-term care facilities and expensive cost of care.