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Background After using sacubitril/valsartan, patients with heart failure exhibit different degrees of reverse cardiac remodeling. Those with unsatisfactory improvement may derive more harm than benefit because sacubitril/valsartan may impair renal function. This study investigated the critical factors related to changes in left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) in patients to help clinicians balance the efficacy and safety of sacubitril/valsartan. Methods This retrospective study observed 333 patients with baseline LVEF ≤ 40% who had been prescribed sacubitril/valsartan for ≥ 30 days. We recorded their echocardiographic and laboratory data at 6-month intervals. The endpoint was death or heart transplantation. Results The median follow-up was 33.1 months. At 6 months, the mean increase in LVEF was 5.04%. Compared with the patients with a ∆LVEF of < 5% at 6 months, the patients with a ∆LVEF of ≥ 5% had a significantly higher survival rate, a shorter average heart failure duration, a lower rate of diuretic use at baseline, and better renal function at 6 months. The patients’ eGFR declined at an average rate of − 2.8 mL/min/1.73 m2 per year. Compared with the patients with a ∆eGFR of < 20% at 6 months, the patients with a ∆eGFR of ≥ 20% had a significantly lower survival rate, higher blood urea nitrogen and pulmonary pressure at baseline, and a higher average dose of concomitant diuretics at 6 months. Conclusion Although LVEF increasing ≥ 5% is associated with favorable health outcomes, eGFR decreasing ≥ 20% within the first 6 months of initiating sacubitril/valsartan is an indication against titration.