BACKGROUND: Epicardial adipose tissue (EAT) is an emerging cardio-metabolic risk factor and has been shown to correlate with adverse cardiovascular (CV) outcome; however the underlying pathophysiology of this link is not well understood. The aim of this study was to evaluate the relationship between EAT and a comprehensive panel of cardiovascular risk biomarkers and pulse wave velocity (PWV) and indexed left ventricular mass (LVMI) in a cohort of patients with cardiovascular disease (CVD) and diabetes compared to controls. METHODS: One hundred forty-five participants (mean age 63.9 ± 8.1 years; 61% male) were evaluated. All patients underwent cardiovascular magnetic resonance (CMR) examination and PWV. EAT measurements from CMR were performed on the 4-chamber view. Blood samples were taken and a range of CV biomarkers was evaluated. RESULTS: EAT measurements were significantly higher in the groups with CVD, with or without T2DM compared to patients without CVD or T2DM (group 1 EAT 15.9 ± 5.5 cm2 vs. group 4 EAT 11.8 ± 4.1 cm2, p = 0.001; group 3 EAT 15.1 ± 4.3 cm2 vs. group 4 EAT 11.8 ± 4.1 cm2, p = 0.024). EAT was independently associated with IL-6 (beta 0.2, p = 0.019). When added to clinical variables, both EAT (beta 0.16, p = 0.035) and IL-6 (beta 0.26, p = 0.003) were independently associated with PWV. EAT was significantly associated with LVMI in a univariable analysis but not when added to significant clinical variables. CONCLUSIONS: In patients with cardio-metabolic disease, EAT was independently associated with PWV. EAT may be associated with CVD risk due to an increase in systemic vascular inflammation. Whether targeting EAT may reduce inflammation and/or cardiovascular risk should be evaluated in prospective studies.