There is a disproportionate burden and severity of heart failure (HF) among black patients (pts) who may be less responsive to treatment with an ACEi/ARB than other racial/ethnic groups. How black pts with HF respond to sacubitril/valsartan (S/V), an angiotensin receptor neprilysin inhibitor, has not been fully explored. The PIONEER-HF trial was a prospective, multicenter, double-blind, active-controlled, randomized trial which enrolled 881 pts at 129 sites in the United States. Pts with or without a history of prior HF and an EF ≤40% and an NT-proBNP ≥1600 pg/mL or BNP ≥400 pg/mL were eligible for participation no earlier than 24 hours and after hemodynamic stabilization while hospitalized for acute decompensated HF (ADHF). Pts were randomly assigned 1:1 to in-hospital initiation of S/V (N = 440) vs. enalapril (E, N = 441) for 8 weeks. We performed a pre-specified subgroup analysis by self-reported race (i.e., black vs. other). The study population was 316 (35.9%) black, 515 (58.5%) white, and 50 (5.7%) other. Black pts (Ratio of change ROC 0.72, 95% CI 0.57-0.89) experienced a similar improvement in NT-proBNP with S/V vs. E compared to white pts (ROC 0.68, 95% CI 0.58-0.80; p-value for interaction = 0.13). There was no statistical interaction between race and the effect of S/V on the composite of CV death or rehospitalization for HF (black: HR 0.47, 95% CI 0.24-0.94 vs. white: HR 0.60, 95% CI 0.35-1.01) (Figure). The incidence of worsening renal function, hyperkalemia, and symptomatic hypotension was comparable with S/V vs. E regardless of race. There was one confirmed angioedema event in the S/V arm (in a white pt), while there were six in the enalapril arm (all in black pts) (p-value = NS). Among black pts admitted for ADHF, in-hospital initiation of S/V resulted in a greater reduction in natriuretic peptide levels, was safe and well-tolerated, and led to a significant improvement in clinical outcomes compared to enalapril. The effect of S/V vs. E on these outcomes did not differ by race. No angioedema event with S/V was observed in a black patient.