Background: Myocardial infarction (MI) remains the leading cause of death worldwide, especially when combined with type 2 diabetes mellitus (T2DM). Many trials have established the cardiovascular benefits of Sodium-Glucose cotransporter 2 inhibitors (SGLT-2i) in diabetic patients at high cardiovascular risk. Aim: To evaluate the cardioprotective effect of SGLT-2I in STEMI diabetic patients undergoing primary percutaneous coronary intervention. Patients and methods: This Comparative cross-sectional study was conducted on 30 diabetic patients with ST segment elevation myocardial infarction (STEMI) undergoing Primary PCI, at Cardiology department, Zagazig University hospital. Based on admission antidiabetic therapy; the patients were equally divided into diabetic patients not on SGLT2I, and second group diabetic patients on SGLT2I (including Empagliflozin and Dapagliflozin). Results: The current study showed hs-TnI levels (I hs-TnI, II hs-TnI, III hs-TnI and hs-TnI peak) were significantly higher in non SGLT2I group compared to SGLT2I group (P<0.05), with no significant difference between both groups regarding CK-MB, also WMSI was significantly higher in non SGLT2I group compared to SGLT2I group (P=0.007). Incidence of all cause death was significantly higher in non SGLT2I group compared to SGLT2I group (P=0.027). HF hospitalization was significantly higher in non SGLT2I group compared to SGLT2I group (P=0.010). MACE was significantly higher in non SGLT2I group compared to SGLT2I group (P=0.022). The multivariate regression analysis revealed that hs-TnI peak, serum creatinine after 24 hr., mitral regurgitation on discharge, and complete revascularization were the only significant predictors of cardiovascular death. The multivariate regression analysis revealed that serum creatinine after 24 hr., mitral regurgitation on discharge, complete revascularization and receiving SGLT2-I were the only significant predictors of MACE. The multivariate regression analysis revealed that complete revascularization and receiving SGLT2-I was the only significant predictors of HF hospitalization. Conclusion: In diabetic patients with AMI, the use of SGLT2 inhibitors was associated with a documented cardioprotecton.