Objective: The medication regimen of elderly patients with heart failure (HF) was analyzed concretely, and the effect of Sacubitril Valsartan on it was evaluated. Methods: This study was a prospective trial. A total of 120 elderly patients treated at our hospital for HF were sampled. During September 2019 to March 2021, 60 patients in the control group were cured with conventional anti-HF drugs (benazepril + bisoprolol + spironolactone). In the observation group, 60 cases were cured with Sacubitril Valsartan combined with conventional anti-HF drugs (bisoprolol + spironolactone). The therapeutic indexes were observed and the efficacy and safety of various regimes were evaluated. Results: The total effective rate of the observation group (95.00%) was higher compared to the control group (81.67%), and the rate of rehospitalization within one year (3.33%) was lower compared to the control group (13.33%). After treatment, left ventricular ejection fraction (LVEF) in the observation group was higher, left ventricular end-diastolic diameter while (LVEDD) and left ventricular end-systolic diameter (LVESD) in the observation group were lower. Nitric oxide (NO) and flow-mediated vasodilation function of brachial artery (FMD) in the observation group were higher, and serum endothelin-1 (ET-1) was lower. After treatment, creatine kinase (CK), aspartate aminotransferase (AST) and creatine kinase isoenzyme (CK-MB) in the observation group were lower, and intercellular adhesion factor-1 (ICAM-1) and tumor necrosis factor-α (TNF- α) in the observation group were lower. An analysis of adverse reactions revealed no remarkable differences (P>0.05). Conclusion: It is difficult to enhance the condition of elderly patients with HF with conventional anti-HF drugs alone, and it has a better effect and has no effect on the safety of drug use.