Objective To observe the efficacy of sacubitril/valsartan (Sac/Val) in the treatment of patients with type II cardiorenal syndrome (CRS) and its influence on ambulatory electrocardiogram (AECG) heart rate and levels of serum cystatin.-C (Cys.-C), N.-terminal pro.-brain natriuretic peptide (NT.-proBNP) and cardiac troponin T (cTnT). Methods 108 patients with type II CRS admitted from August 2021 to August 2023 were selected and classified into 54 cases in Val group (conventional treatment + Val) and 54 cases in Sac/Val group (Sac/Val on the basis of control) by the random number table method. The efficacy after treatment and changes of AECG heart rate ［standard deviation of of NN intervals within 24 h (SDNN), percentage of adjacent normal.-to.-normal interval with standard deviation of ≥50 ms (PNN50), root mean square of successive differences (rMSSD), standard deviation of the average normal.-to.-normal intervals for each of the 5 min segments (SDANN)］, cardiac function ［left ventricular end.-diastolic diameter (LVEDD), left ventricular end.-systolic diameter (LVESD)］ and renal function ［glomerular filtration rate (GFR), serum creatinine (Scr), blood urea nitrogen (BUN)］ and Cys.-C, NT.-proBNP and cTnT levels before and after treatment were compared between both groups, and the adverse reactions were recorded. 〖WTHZ〗Results The efficacy in Sac/Val group was higher than that in Val group (P＜0.05). Before treatment, there were no obvious differences in AECG heart rate, cardiac function, renal function, Cys.-C, NT.-proBNP and cTnT between the two groups (P＞0.05). After treatment, the SDNN, rMSSD, SDANN and PNN50 in both groups were risen compared with those before treatment (P＜0.05) while the LVEDD and LVESD were reduced (P＜0.05), and the GFR was increased (P＜0.05) while the Scr and BUN were enhanced compared to before treatment (P＜0.05), and the levels of Cys.-C, NT.-proBNP and cTnT were lowered in the two groups than those before treatment (P＜0.05), and there were obvious differences between Sac/Val group and Val group (P＜0.05). The adverse reaction revealed no statistical significance between the two groups (P＞0.05). Conclusion Sacubitril/valsartan has a significant efficacy in treating CRS, and it can effectively improve the AECG heart rate and cardiorenal function, and reduce the levels of serum Cys.-C, NT.-proBNP and cTnT