Abstract: 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 end-diastolic 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 （χ ² = 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.