Abstract Objective: To investigate the clinical effect of daglipzin in patients with heart failure and its effect on vascular endothelial function. Methods: 98 patients with heart failure admitted to our hospital from June 2022 to June 2024 were selected as the study objects. Patients were divided into control group (49 cases) and study group (49 cases) according to random number table method. The control group was treated with sacubactril and valsartan sodium. The study group was treated with daglipzin on the basis of the control group. The efficacy, vascular endothelial function [brachial artery endothelium-dependent diastolic function (FMD), independent diastolic function (NMD), nitric oxide (NO), endothelin-1 (ET-1)] and clinical safety of the two groups were analyzed and compared. Results: The total effective rate of the study group was significantly higher than that of the control group (P < 0.05). After treatment, the levels of FMD, NMD and NO in 2 groups were significantly increased compared with before treatment, and the level of ET-1 was significantly decreased compared with before treatment (P < 0.05). After treatment, the levels of FMD, NMD and NO in the study group were significantly higher than those in the control group, and the level of ET-1 was significantly lower than that in the control group (P < 0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (P > 0.05). Conclusion: In patients with heart failure, the combination of dagaglizin and sacubatrotril valsartan sodium can improve the clinical efficacy and vascular endothelial function, and the clinical safety is good.