BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is a chronic disease with substantial mortality. Management of HFrEF has seen significant breakthrough after the launch of neprilysin inhibitor. The PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impacton Global Mortality and Morbidity in Heart Failure) trial showed that sacubitril/valsartan significantly reduces HFrEF mortality and the heart failure hospitalization rate. However, in patients with advanced kidney disease, who have the highest prevalence of heart failure, the efficacy and safety of sacubitril/valsartan remains uncertain. We aim to study the efficiency of sacubitril/valsartan in patients with end-stage kidney disease. METHODS AND RESULTS: Heart function was screened by echocardiogram among all patients with end-stage kidney disease in 2 hospitals. Patients with HFrEF received either sacubitril/valsartan or conventional treatment. Fifteen echocardiographic parameters were compared before and after treatment. After 1-year sacubitril/valsartan treatment, parameters of systolic (left ventricular ejection fraction 31.3% to 45.1%, P<0.0001; left ventricular end-systolic volume 95.7 to 70.1 mL, P=0.006; left ventricular internal diameter at end-systole phase 47.2 to 40.1 mm, P=0.005), and diastolic (E/A ratio 1.3 to 0.8, P=0.009; E/ Med e’ ratio 25.3 to 18.8, P=0.010) function improved in patients with HFrEF and end-stage kidney disease. These parameters were unchanged in the conventional treatment group. Serum potassium did not increase in the sacubitril/valsartan group. CONCLUSIONS: Sacubitril/valsartan improves left ventricular systolic and diastolic function in patients with HFrEF and end-stage kidney disease.