Objective: Among patients with estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 and left ventricular ejection fraction (LVEF) < 40%, 31 patients who received ARNi were enrolled from August 2018 to April 2020. As a control group, 31 age- and sex-matched cohort who received renin-angiotensin-aldosterone system inhibitor (RAASi) with eGFR < 30 ml/min/1.73m2 and LVEF < 40% were selected. We compared efficacy and safety of ARNI at 12 months. The primary outcome was four-point major adverse cardiovascular events (MACE), composite of death from cardiovascular disease, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Methods: In total of 62 patients, the mean eGFR was 15.8 ± 9.7 ml/min/1.73m2 and the mean LVEF was 29.8 ± 7.5%. There were 26 dialysis patients (41.9%) in the study cohort. At 12 months, there was no significant difference in LVEF between two groups, but MACE was significantly lower in ARNi group than RAASi group (12.9% vs. 35.5%, respectively, p = 0.038). The Kaplan-Meier curves showed that cumulative incidence of MACE was lower in the ARNi group than in the RAASi group (p = 0.043). The incidence of hyperkalemia was comparable between two groups. In non-dialysis cohort, there were no significant differences in the decrease of eGFR and development of hyperkalemia between two groups. Results: This study showed that ARNi might improve cardiovascular outcomes in patients with advanced chronic kidney disease. Further clinical trials are warranted. Conclusions: Objective: Patients with chronic kidney disease are at increased risk of cardiovascular events. Recently, angiotensin receptor-neprilysin inhibitor (ARNi) led to a reduced risk of heart failure hospitalization and cardiovascular mortality among patients with heart failure with reduced ejection fraction. However, there are few studies regarding ARNi in patients with advanced chronic kidney disease. Methods: Among patients with estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 and left ventricular ejection fraction (LVEF) < 40%, 31 patients who received ARNi were enrolled from August 2018 to April 2020. As a control group, 31 age- and sex-matched cohort who received renin-angiotensin-aldosterone system inhibitor (RAASi) with eGFR < 30 ml/min/1.73m2 and LVEF < 40% were selected. We compared efficacy and safety of ARNI at 12 months. The primary outcome was four-point major adverse cardiovascular events (MACE), composite of death from cardiovascular disease, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Results: In total of 62 patients, the mean eGFR was 15.8 ± 9.7 ml/min/1.73m2 and the mean LVEF was 29.8 ± 7.5%. There were 26 dialysis patients (41.9%) in the study cohort. At 12 months, there was no significant difference in LVEF between two groups, but MACE was significantly lower in ARNi group than RAASi group (12.9% vs. 35.5%, respectively, p = 0.038). The Kaplan-Meier curves showed that cumulative incidence of MACE was lower in the ARNi group than in the RAASi group (p = 0.043). The incidence of hyperkalemia was comparable between two groups. In non-dialysis cohort, there were no significant differences in the decrease of eGFR and development of hyperkalemia between two groups. Conclusions: This study showed that ARNi might improve cardiovascular outcomes in patients with advanced chronic kidney disease. Further clinical trials are warranted.