Objective: To explore the clinical efficacy and safety of sacubitril/valsartan combined with sildenafil in the treatment of patients with right heart failure caused by pulmonary arterial hypertension (PAH). Method: 72 patients with right heart failure caused by pulmonary hypertension who visited our hospital from March 2024 to March 2025 were selected as the research subjects. The patients were divided into the control group and the combined group by random number table method, with 36 cases in each group. The control group was treated with sildenafil. The combination group was treated with sacubitril/valsartan combined with sildenafil. The clinical efficacy, cardiac function [right ventricular diameter (RVD), pulmonary artery systolic pressure (PASP), right ventricular ejection fraction (RVEF), left ventricular ejection fraction (LVEF)], and blood biochemical indicators [N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin I (cTnI), endothelin-1 (ET-1), nitric oxide (NO)], exercise endurance [6-minute walking distance (6 MWD)] and the occurrence of adverse reactions of the two groups were analyzed and compared. Result: The total effective rate of treatment in the combined group was significantly higher than that in the control group (P < 0.05). After treatment, the RVD and PASP levels in both groups were significantly lower than those before treatment, while the RVEF and LVEF levels were significantly higher than those before treatment. Moreover, the RVD and PASP levels in the combined group were significantly lower than those in the control group, and the RVEF and LVEF levels were significantly higher than those in the control group (P<0.05). After treatment, the levels of NT-proBNP, cTnI and ET-1 in both groups were significantly lower than those before treatment, and the level of NO was significantly higher than that before treatment. Moreover, the levels of NT-proBNP, cTnI and ET-1 in the combined group were significantly lower than those in the control group, and the level of NO was significantly higher than that in the control group (P<0.05). After treatment, the 6MWD of both groups was significantly increased compared with that before treatment, and the 6MWD of the combined group was significantly greater than that of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Sacubitril/valsartan combined with sildenafil in the treatment of right heart failure caused by PAH can improve the therapeutic effect, enhance cardiac function, reduce pulmonary vascular load, repair vascular endothelial function, increase exercise endurance, and has good safety.