This study aimed to assess the utility of echocardiography-measured epicardial adipose tissue (EAT) thickness (EATT) as an independent predictor for coronary artery disease (CAD), examining its correlation with oxidative stress levels in epicardial tissue and the complexity of the disease in patients undergoing open-heart surgery. This study included a total of 25 patients referred for cardiac surgery with 14 in the CAD group and 11 in the non-CAD group. Epicardial fat was sampled from patients subjected to open-heart surgery. EATT was higher in the CAD group compared to the non-CAD group (8.15±2.09mm vs. 5.12±1.8mm, p=0.001). The epicardial reactive oxygen species level was higher in the CAD group compared to the non-CAD group (21.4±2.47nmol H2O2/g tisssue/h vs. 15.7±1.55nmol H2O2/g tisssue/h, p<0.001). EATT greater than 6.05mm was associated with CAD, with a sensitivity of 86% and specificity of 73%. Echocardiographically measured EATT is a significant, independent predictor of CAD. Its relationship with increased EAT oxidative stress levels suggests a potential mechanistic link between EATT and CAD pathogenesis. These findings highlight the importance of EATT as a diagnostic tool in assessing the complexity of CAD in patients undergoing cardiac surgery.