Objective To observe the effect of sacubitril/valsartan on renal function in patients with chronic heart failure (CHF) and renal insufficiency. Methods A total of 84 consecutive CHF patients with renal insufficiency who visited the First Hospital of Qinhuangdao form December 2020 to March 2022 were enrolled and divided into sacubitril/valsartan group (n=48) and control group (n=36). The sacubitril/valsartan group received sacubitril/valsartan and the control group received single valsartan. The two groups were observed for the changes in serum creatinine, estimated glomerular filtration rate (eGFR), urea nitrogen, uric acid, and worsening renal function (WRF) at 6 and 12 months after medication. SPSS statistics 22.0 was used for statistical analysis. Data comparison between two groups was perfomed using t test, non-parametric rank sum test, non-parametric test, Mann-Whitney U test or χ² test depending on data type. Results At 6 months, there were no significant differences in serum creatinine (P=0.254) and eGFR (P=0.061) in comparison with the baseline between the two groups. The decreased values of urea nitrogen [-2.62 (1.83,3.90) vs 0.45 (0.29,0.70) mmol/L; P<0.01] and uric acid [-137.00(-92.30,-201.13) vs -9.65(49.00,-79.80) μmol/L; P =0.000] were significantly higher in the sacubitril/valsartan group than those in the control group. Compared with the control group, sacubitril/valsartan reduced systolic blood pressure [(132±17) vs (133±24) mmHg (1mmHg=0.133kPa); P=0.824] and diastolic blood pressure [(81±14) vs (82±12) mmHg; P=0.732], but there was no statistical differences. NYHA classification was significantly improved between two groups (Z=-2.150; P=0.032). Compared with the baseline at, 12 months, the decline of eGFR was lower in the sacubitril/valsartan group than the control group [-2.21 (1.33,3.49) vs -22.11 (12.32,29.67) ml/(min·1.73 m²); P=0.023]; the increase in serum creatinine was significantly lower in the sacubitril/valsartan group than in the control group [1.50 (0.98,2.07) vs 31.65 (22.77,42.53) μmol/L; P=0.043]; the decreases in urea nitrogen [-2.80 (2.01,4.23) vs 0.80 (0.58,1.14) mmol/L; P<0.01] and uric acid [-141.00(-96.40,-200.25) vs -8.45(45.00,-77.70) μmol/L; P=0.011] were significantly higher in the the sacubitril/valsartan group than in the control group. The sacubitril/valsartan group had a significantly greater reduction in systolic blood pressure [(123±14) vs (130±17) mmHg; P=0.042] and diastolic blood pressure [(76±11) vs (81±11) mmHg; P=0.042] and significantly better NYHA classification (Z=-2.200; P=0.028) than the control group. There was no significant difference in the incidence of WRF [3 (6.25%) vs 7 (19.44%); P=0.132] between the two groups at 6 months, but at 12 months, the incidence of WRF in the sacubitril/valsartan group is significantly lower than that in the control group [4 (8.33%) vs 9 (25.00%); P=0.037]. Conclusion In the sacubitril/valsartan group, improvement in cardiac function precedes the effect of renal protection, and blood pressure decreases simultaneously with effect of renal protection. Compared with single valsartan, sacubitril/valsartan can delay and control the worsening of renal function in CHF patients with renal insufficiency and reduce the occurrence of WRF. The renal protective effect of sacubitril/valsartan is more significant with the prolongation of medication.