Objective The aim of this study was to evaluate the efficacy and side effects of sacubitril/valsartan in the treatment of patients with chronic kidney disease （CKD） at stage 5 with resistant hypertension， and to explore the cardiovascular benefits and security of medical in the patients. Methods Patients with CKD5 resistant hypertension diagnosed and treated in the First Affiliated Hospital of Guangxi Medical University from September 2020 to March 2022 were selected and divided into the observation group （treated with routine treatment of kidney disease at end-stage and sacubitril/valsartan） and control group （include droutine treatment of renal disease at end-stage and ACEI or ARB drugs） according to treatment strategy. The patients in both two groups were treated with adequate dialysis treatment and conventional drug treatment of renal disease at end-stage. The patients were followed up for at least 3 months，the clinical efficacy of three months after treated with sacubitril/valsartan was observed， and the efficacy indicators and security indicators and adverse cardiovascular events were observed， the occurrence of adverse effects during the period of drug use were compared with the control group. Results A total of 110 patients were included in this study and there were 55 cases in each group.There were no significant differences in gender， age， age of dialysis， etiology， dialysis mode and blood pressure between the two groups （P > 0.05）. The Systolic blood pressure （SBP）， diastolic blood pressure （DBP）， b-type urinary natriuretic peptide precursor （Pro-BNP） and cardiac function grade in the observation group after treatment was significantly decreased compared with before treatment. The left ventricular ejection fraction （LVEF） and the ratio of LVEF < 50% in the observation group was significantly reduced after treatment （P < 0.05）. SBP， DBP and Pro-BNP decreased 3 months after treatment compared with the baseline before treatment，and improved significantly in the first month after treatment（P < 0.05）. The decrease of DBP and BNP before and after treatment was significantly different between the two groups， and the decrease of DBP and BNP was more significant in the observation group（P < 0.05）. The difference of LVEF and left ventricular end diastolic diameter （LVEDD）between the two groups before and after treatment was statistically significant， and the improvement was more obvious in the observation group （P < 0.05）. There were no significant differences in the safety indicators of serum potassium， estimated glomerular filtration rate （eGFR） and liver function between two groups before and after treatment （P > 0.05）. In terms of adverse reactions， only 1 case in the control group developed hyperkalemia within 3 months of follow-up， and no hypotension or other adverse reactions occurred in the two groups. Conclusions The treatment of patients with CKD stage 5 hypertension with sacubitril/valsartan has obvious cardiovascular benefits. Sacubitril/Valsartan has efficacy in lowering blood pressure， improving cardiac function and reducing volume load， with less adverse events and higher safety than control group.