Epicardial adipose tissue (EAT) is a significant source of inflammatory mediators in patients with critical coronary artery disease (CAD). This study compared the expression of inflammatory mediators in EAT and subcutaneous adipose tissue (SAT) in 42 patients undergoing coronary artery bypass grafting (CABG). Results showed significantly higher levels of IL-1β, IL-6, MCP-1, and TNF-α in EAT compared to SAT, both at the mRNA and protein levels. These findings were consistent across various clinical variables and plasma biomarkers, indicating that EAT inflammation is independent of traditional risk factors such as obesity, diabetes, or statin use. Microarray analysis confirmed a broad inflammatory response in EAT, with upregulated genes related to inflammation and immune response. Inflammatory cell infiltrates were also observed in EAT, suggesting a proinflammatory environment. The study highlights that EAT is a significant source of inflammatory mediators, and conventional therapies may not adequately reduce local inflammation. Plasma inflammatory biomarkers may not fully reflect local tissue inflammation, emphasizing the need for targeted interventions to address EAT inflammation. The study underscores the role of EAT in cardiovascular disease progression and the importance of understanding its inflammatory properties for developing effective therapeutic strategies.Epicardial adipose tissue (EAT) is a significant source of inflammatory mediators in patients with critical coronary artery disease (CAD). This study compared the expression of inflammatory mediators in EAT and subcutaneous adipose tissue (SAT) in 42 patients undergoing coronary artery bypass grafting (CABG). Results showed significantly higher levels of IL-1β, IL-6, MCP-1, and TNF-α in EAT compared to SAT, both at the mRNA and protein levels. These findings were consistent across various clinical variables and plasma biomarkers, indicating that EAT inflammation is independent of traditional risk factors such as obesity, diabetes, or statin use. Microarray analysis confirmed a broad inflammatory response in EAT, with upregulated genes related to inflammation and immune response. Inflammatory cell infiltrates were also observed in EAT, suggesting a proinflammatory environment. The study highlights that EAT is a significant source of inflammatory mediators, and conventional therapies may not adequately reduce local inflammation. Plasma inflammatory biomarkers may not fully reflect local tissue inflammation, emphasizing the need for targeted interventions to address EAT inflammation. The study underscores the role of EAT in cardiovascular disease progression and the importance of understanding its inflammatory properties for developing effective therapeutic strategies.