The purpose of this study was to investigate the efficacy of sacubitril/valsartan sodium combined with metoprolol tartrate for chronic heart failure (CHF) and its relation with vascular endothelial function and neuroendocrine function. A total 96 patients with CHF were divided into control group (48 cases) and observation group (48 cases), which received treatment using metoprolol tartrate and sacubitril/valsartan sodium combined with metoprolol tartrate for three months, respectively. After treatment, the total effective rate in observation group was significantly higher than control group (p < 0.05). Compared with control group, in observation group the left ventricular ejection fraction was obviously increased, the left ventricular end-diastolic diameter and left ventricular end-systolic diameter were obviously decreased, the 6-min walking distance and Activity of Daily Living Scale score were obviously increased, the serum nitric oxide and nitric oxide synthase levels were obviously increased, and the serum endothelin-1, N-terminal pro-brain natriuretic peptide, angiotensin II and aldosterone levels were obviously decreased (all p < 0.05). In conclusion, in treatment of CHF, sacubitril/valsartan sodium combined with metoprolol tartrate can effectively enhance the cardiac function, exercise tolerance and self-care ability, and improve the vascular endothelial function and neuroendocrine function.