BACKGROUND Leptin is an adipokine related to overweight and cardiovascular diseases. However, the leptin expression level in epicardial adipose tissue (EAT) of humans and its association with coronary atherosclerosis has never been investigated. MATERIAL AND METHODS Patients receiving cardiac surgery were divided into a coronary artery disease group (CAD group) and a non-CAD group (NCAD group). Blood samples from coronary vein, biopsies of subcutaneous adipose tissue (SAT), and EAT were acquired during the surgery. Serum leptin level and leptin level in EAT and SAT were tested with ELISA, quantitative PCR, and immunohistochemistry and were compared between the CAD group and NCAD group, as well as between stenosis and non-stenosis subgroups. Logistic regression analysis was performed to explore the risk factors for coronary artery stenosis. RESULTS No statistically significant differences were found in demographic and clinical data between groups (all P>0.05). Serum leptin concentration and leptin expression in EAT and SAT of the CAD group were much higher in than in the NCAD group (all P<0.05). In subgroup analysis, there was no difference in serum leptin and expression in SAT of stenosis and non-stenosis patients (All P>0.05). The leptin expression level in EAT of stenosis patients was significantly higher than in non-stenosis patients (P=0.0431). By multivariate logistic regression analysis, we demonstrated that leptin expression level in EAT was an independent risk factor for coronary artery stenosis [OR=1.09, 95%CI (1.01±1.18), P=0.031]. CONCLUSIONS Leptin expression in EAT and SAT were both increased for CAD patients. Leptin expression in EAT was an independent risk factor for coronary atherosclerosis in the adjacent artery, while leptin in SAT was not associated.