Cardiovascular disease is on the rise globally, with ischemic heart disease being the leading cause of mortality and morbidity. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve cardiovascular outcomes in patients with heart failure, evidence is limited in guiding initiation in post-acute myocardial infarction (post-AMI) patients. Hence, this study aimed to appraise the current literature on the effect of SGLT2i on the clinical outcomes of post-AMI patients. A comprehensive search of PubMed, EMBASE, SCOPUS, and ClinicalTrials.gov was conducted up to 1 May 2024. Only randomized controlled trials studying the use of SGLT2i in post-AMI patients were included. We included adult patients aged 18 years old and older diagnosed with AMI and initiated on SGLT2i in the acute post-AMI setting. SGLT2i studies solely in heart failure settingswere excluded. Eight clinical trials were included in the systematic review, comprising 11,436 patients. Compared with placebo, SGLT2i initiation in post-AMI patients significantly reduced total number of heart failure hospitalizations (risk ratio [RR] 0.74, 95% confidence interval [CI] 0.62-0.90) and was associated with a lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (- 26.67 pg/ml, 95% CI - 41.74 to - 11.59). There was no difference in all-cause mortality (RR 1.02, 95% CI 0.81-1.28), cardiovascular mortality (RR 1.03, 95% CI 0.83-1.28), change in left ventricular ejection fraction, and glycated hemoglobin (HbA1c), as compared with placebo. SGLT2i use in patients with AMI was associated with a reduction in heart failure hospitalizations and a decrease in NT-proBNP. There were no significant differences in mortality outcomes. PROSPERO identifier number CRD42024540843.