BACKGROUND: Patients with acute myocardial infarction (MI) complicated by heart failure (HF) are subject to higher mortality during the index hospitalization. Early risk prediction and intervention may help prevent HF-related morbidity and mortality. METHODS AND RESULTS: We examined 77 675 ST-elevation MI and 110 128 non-ST-elevation patients with MI without cardiogenic shock or HF at presentation treated at 609 hospitals in Acute Coronary Treatment and Intervention Outcomes Network Registry (ACTION) Registry-Get With The Guidelines between January 1, 2007, and March 31, 2011. Logistic regression identified patient characteristics associated with development of in-hospital HF. Overall, 3.8% of patients with MI developed in-hospital HF, which was associated with higher mortality in both ST-elevation MI and non-ST elevation MI. In multivariable logistic regression, left ventricular ejection fraction ≤30%, prior HF, diabetes mellitus, female sex, ST-elevation MI, and hypertension (all P<0.005) were independently associated with in-hospital HF. Patients who developed HF during non-ST-elevation MI were more likely to be medically managed without catheterization (30% versus 13% with HF, P<0.0001) or had longer delays to surgical or percutaneous revascularization. Patients with ST-elevation MI and HF were less likely to receive primary percutaneous coronary revascularization (84% versus 79% with HF, P<0.0001), and more likely to receive thrombolytic therapy (14% versus 11%; P=0.0001). CONCLUSIONS: Patients with MI who develop HF during hospitalization have a higher risk clinical profile and greater mortality, but may be less likely to receive revascularization in a timely fashion. Targeting these highest risk patients may improve outcome post-MI.