BACKGROUND: The objective of this study was to prospectively evaluate beta-blocker use at hospital discharge as an indicator of quality of care and outcomes in patients with heart failure (HF). METHODS AND RESULTS: Data from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry for patients hospitalized with HF from 259 hospitals were prospectively collected and analyzed. HF medication contraindications, intolerance, and use at hospital discharge were assessed, along with 60- to 90-day follow-up data in a prespecified cohort. There were 20,118 patients with left ventricular systolic dysfunction. At discharge, 90.6% of patients were eligible to receive beta-blockers, and 83.7% were eligible to receive an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Eligible patients discharged with beta-blockers were significantly more likely to be treated at follow-up than those not discharged with beta-blockers (93.1% vs 30.5%; P < .0001). Discharge use of beta-blockers in eligible patients was associated with a significant reduction in the adjusted risk of death (hazard ratio: 0.48; 95% confidence interval: 0.32-0.74; P < .001) and death/rehospitalization (odds ratio: 0.74; 95% confidence interval: 0.55-0.99; P = .04), although we cannot completely exclude the possibility of residual confounding. CONCLUSIONS: Discharge beta-blocker use in HF appeared to be well tolerated, improved treatment rates, and was associated with substantially lower postdischarge mortality risk. These data provide additional evidence that supports beta-blocker use at hospital discharge in eligible patients as an HF performance measure.