Background Epicardial adipose tissue (EAT) is an atypical fat depot surrounding the heart with a putative role in the development of atherosclerosis. Methods and Results We profiled genes and miRNAs in perivascular EAT and subcutaneous adipose tissue (SAT) of metabolically healthy patients without coronary artery disease (CAD) vs. metabolic patients with CAD. Compared to SAT, a specific tuning of miRNAs and genes points to EAT as a tissue characterized by a metabolically active and pro-inflammatory profile. Then, we depicted both miRNA and gene signatures of EAT in CAD patients, featuring a down-regulation of genes involved in lipid metabolism, mitochondrial function, nuclear receptor transcriptional activity, and an up-regulation of those involved in antigen presentation, chemokine signalling, and inflammation. Finally, using complementary in silico, molecular and biochemical approaches, we identified miR-103-3p as candidate modulator of CCL13 in EAT, and a potential biomarker role for the chemokine CCL13 in CAD. Conclusions EAT in CAD is characterized by changes in the regulation of metabolism and inflammation with miR-103-3p/CCL13 pair as novel putative actors in EAT function and CAD.