Background: T-cadherin, encoded by the CDH13 gene, has a significant relationship with atherosclerosis and coronary heart disease (CHD) initiation and progression. Vascular cell adhesion molecule-1 (VCAM-1) plays an essential role in endothelial inflammation. Both T-cadherin and VCAM-1 were associated with the occurrence of ST-elevation myocardial infarction (STEMI). Objective: We aimed to find the relationship between CDH13 and VCAM-1 gene expression in STEMI and to evaluate the ability of their gene expression to predict the prognostic outcome of coronary artery disease (CAD) in acute STEMI. Methods: This case-control study enrolled 150 participants: 75 patients with STEMI and 75 healthy controls. A follow up of patients for 6 months was performed. The participants were compared regarding CDH13 and VCAM-1 gene expression, as well as their 6-month clinical outcome. Results: CDH13 and VCAM-1 were significantly elevated in patients with STEMI. Additionally, combined gene expression was significantly superior to single gene expression in predicting the extent of CAD with a Gensini score ≥ 20 at a cut-off value of 5.12 with a sensitivity of 89.5%. Conclusion Combining CDH13 and VCAM-1 expression is more valuable than using them individually in predicting the occurrence of major cardiac events (MACE) and predicting the extent of CAD.