Abstract Background Predischarge β-blocker initiation in hospitalized patients with heart failure due to reduced left ventricular ejection fraction (LVEF) is safe and improves adherence; improved outcomes with this approach have not been demonstrated in a randomized trial. This study compared 6-month rehospitalization rates among patients assigned to predischarge β-blockade coupled with postdischarge nurse management (intervention) versus usual care. Methods and Results We randomized 64 patients with an LVEF ≤0.40 to low-dose carvedilol coupled with nurse management or usual care. The nurse manager saw patients within 2 weeks of discharge, then biweekly until stable. Baseline characteristics reflected a vulnerable population (80% uninsured, 72% minorities, 80% unemployed or disabled), as did heart failure etiology (28% substance abuse, 27% ischemic, 19% hypertension, 17% idiopathic). Mean baseline LVEF was 0.23 in both groups. Among intervention patients at 6 -months, β-blocker utilization was higher (96 vs. 48%, P < .001), mean New York Heart Association class improved (–1.44 vs. –0.77, P = .01), and total heart failure rehospitalizations were reduced by 84% (3 vs. 19, P = .02). A trend toward improved LVEF was also observed (+16 vs. +11 units, P = .17). Conclusion Inpatient β-blocker initiation coupled with nurse management improved outcomes among sociodemographically disadvantaged heart failure patients. Our results support a practice shift toward inpatient β-blocker initiation with structured outpatient follow-up.