Objective To evaluate the clinical efficacy of sacubitril/valsartan in the treatment of acute ST-segment elevation myocardial infarction (STEMI) complicated with heart failure preserved ejection fraction (HFpEF) . Methods A total of 120 STEMI patients complicated with HFpEF were selected and randomly divided into the treatment and control groups. In the treatment group, patients were treated with sacubitril/valsartan and their counterparts in the control group were treated with valsartan for 6 months. The resting heart rate (HR), laboratory indexe (plasma N-terminal type B natriuretic peptide precursor (NT-proBNP) concentration, serum growth and differentiation factor-15 (GDF-15) concentration and serum cyclophilin A (CypA) concentration), left ventricular diastolic function indexes (left atrial volume index (LAVI), the ratio of early diastolic mitral valve flow velocity and early diastolic mitral valve ring movement velocity (E/e) ), ultrasound cardiogram (UCG) indexes (left ventricular ejection fraction (LVEF), left ventricular posterior wall thickness (LVPW), left ventricular end-systolic internal diameter (LVESD) and left ventricular enddiastolic internal diameter (LVEDD) ), and adverse events occurring during follow-up were recorded between two groups before and 1, 3 and 6 months after treatment with sacubitril/valsartan. Results In two groups, the resting HR was improved at 1, 3 and 6 months after corresponding treatment, and no significant difference was observed in the resting HR at the same time points between two groups (all P > 0.05) . At 1, 3 and 6 months after treatment, NT-proBNP, GDF-15 and CypA levels and LVEF in the treatment group were significantly improved compared to the control group, and the differences were statistically significant (all P < 0.05) . At 3 and 6 months after treatment, the left ventricular diastolic function indexes (LAVI and E/e) and UCG indexes (LVPW, LVESD and LVEDD) were more significantly improved than those in the control group, and the differences were statistically significant (all P < 0.05) . The incidence of adverse events (sleep disorder, palpitation and hypotension) was not significantly different between two groups (χ2 = 2.679,P = 0.749) . Conclusions Application of sacubitril/valsartanis an efficacious and safe treatment for STEMI patients complicated with HFpEF, which can effectively improve left ventricular diastolic function, enhance left ventricular remodeling and inhibit inflammatory response. [ABSTRACT FROM AUTHOR]