Objective To determine the effect of dapagliflozin and sacubitril/valsartan on prognosis of patients with heart failure based on propensity score matching. Methods Clinical data of 369 patients with heart failure diagnosed in the First Hospital of Shanxi Medical University from June 2018 to December 2021 were collected and analyzed retrospectively in this study. According to the treatment they received, the subjects were divided into dapagliflozin group and sacubitril/valsartan group. After propensity score matching, the prognosis of the two groups was compared and the influencing factors were analyzed. SPSS statistics 26.0 and R Studio (version 4.1.2) were used for data analysis. Data comparison between two groups was conducted using student′s t test, rank sum test, Chi-square test or Fisher exact probability method depending on data type. Cox regression models were used to analyze the influencing factors for prognosis in two groups of patients, and Kaplan-Meier curves were plotted. Results There were 70 patients in each group after propensity score matching. Kaplan-Meier survival analysis showed no statistical difference in first heart failure rehospitalization after discharge between the two groups (P=0.190). Cox multivariate analysis showed that the New York Heart Association (NYHA) classification (HR=6.923,95%CI=1.032-46.426; P=0.046), left ventricular end diastolic diameter (LVEDD) (HR=1.139,95%CI=1.004-1.293; P=0.044) and Z score of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (HR=1.825,95%CI=1.075-3.097; P=0.026) were prognostic risk factors for patients with heart failure. Alcohol drinking (HR=0.086,95%CI=0.018-0.413; P=0.002) and high-density lipoprotein cholesterol (HDL-C) (HR=0.012,95%CI=0.000-0.642; P=0.029) were prognostic protective factors in the dapagliflozin group. For the sakubatril/valsartan group, smoking (HR=14.376,95%CI=1.657-124.748; P=0.016) was a risk factor, while drinking (HR=0.082,95%CI=0.012-0.578; P=0.012) and hemoglobin (Hb, HR=0.953,95%CI=0.912-0.995; P=0.030) were protective factors. Conclusion After propensity score matching, NYHA classification, LVEDD, Z score of NT-proBNP, HDL-C and alcohol drinking are factors influencing the prognosis of patients with heart failure in the dapagliflozin group. Smoking, Hb and alcohol drinking are prognostic factors in the sakubatril/valsartan group. There is no significant difference in prognosis for heart failure in comparison of dapagliflozin and sakubatril/valsartan.