Empagliflozin, a sodium-glucose cotransporter 2(SGLT2) inhibitor, improves cardiovascular outcomes in heart failure patients, butdata regarding the efficacy of empagliflozin in the setting of acute myocardial infarction (AMI) isstill unclear. The current study aimed to evaluate whether treatment with empagliflozin before primary percutaneous coronary intervention (PCI) improves parameters associated with patients' outcomes. We randomly assigned 101 non-diabetic and non-heart failure patients with ST-elevation myocardial infarction (STEMI) who underwent primary PCI to receive either empagliflozin (10 mg before PCI and once daily for 40 days) or placebo, in addition to the standard treatment. The primary outcomes were changes in left ventricular ejection fraction (LVEF) 40 days after PCI, changes in cardiac troponin I(cTnI) and estimates of its area under the curve (AUC) and the peak level, and resolution of ST-segment in > 50% of leads 90 min after PCI. No significant difference was observed in terms of the occurrence of ST-segment resolution > 50% (46.0% versus 45.0%; p = 0.92) and the mean level of cTnI at each time point between the two groups. The estimated mean [standard deviation (SD)] AUC of cTnI was 955.0 (595.7) ng h/ml in the intervention and 999.7 (474.7) ng h/ml in the control groups (p = 0.85) without any significant difference in peak cTnI level. The mean (SD) LVEF 40 days after primary PCI was significantly higher in empagliflozin-treated patients than the placebo group [43.2% (5.8%) versus 39.2% (6.7%); p = 0.002]. In this study, no significant differences wereobserved across the groups in terms of cTnI levels and ST-segment resolution in patients with STEMI undergoing primary PCI. However, it shed light on the potential benefits of empagliflozin in improving LVEF following STEMI. Iranian Registry of Clinical Trials Platform ( https://irct.behdasht.gov.ir/ ) identifier number IRCT20111206008307N42.