Objective To investigate the curative effect of sakubatril-valsartan in patients with hypertension complicated by chronic heart failure (CHF) and its influence on levels of angiotensin Ⅱ (AngⅡ) and fibroblast growth factor 23 (FGF23). Methods The patients (n=76) with essential hypertension (EH) complicated by CHF were chosen from the Third Hospital of Xingtai City from Jan. 2018 to Dec. 2019, and divided into observation group (n=36) and control group (n=35). All groups were given routine treatment, and control group was orally given perindopril and observation group was given sakubatril-valsartan for 4 weeks as one therapeutic course. The treatment was lasted for 3 courses. The clinical efficacy and changes of HF symptoms, echocardiogram, vascular endothelial function and levels of AngII and FGF23 were observed before and after treatment and adverse reactions were recorded during therapeutic period in 2 groups. Results The curative effect rate was higher in observation group than that in control group (91.67% vs. 71.43%, P<0.05). After treatment, the heart rate (HR) decreased significantly and 24 h urine volume increased in 2 groups, and HR was lower and 24 h urine volume was higher in observation group than those in control group (P<0.05). After treatment, left ventricular ejection fraction (LVEF) and 6-minute walk test (6MWT) increased, and left ventricular enddiastolic inner diameter (LVEDD) and N-terminal pro-brain natriuretic peptide (NT-proBNP) decreased in 2 groups than before, and LVEF and 6MWT were higher and LVEDD and NT-proBNP were lower in observation group than those in control group (P<0.05). After treatment, the levels of endothelin-1 (ET-1), AngⅡ and FGF23 decreased, and level of nitric oxide (NO) increased in 2 groups, and levels of ET-1, AngⅡ and FGF23 were lower and NO level was higher in observation group than those in control group (P<0.05). Conclusion Compared with perindopril, sakubatril-valsartan has more significant effects of relieving HF symptoms and improving heart function, vascular endothelial function and FGF23 level with reliable curative effect and higher safety in patients with EH complicated by CHF.