Background: We explored the association of epicardial fat volume (EFV) with coronary plaque characteristics, coronary artery calcification (CAC) score, coronary stenosis, lesion-specific ischemia in patients with known or suspected coronary artery disease (CAD). Methods: 88 controls and 221 patients were analyzed in the study. High-risk plaque was defined as existing >= 2 features, including positive remodeling, low attenuation, napkin-ring sign and spotty calcification. EFV, CAC score was measured. The severity of coronary stenosis was quantified using Gensini score. CT-FFR was performed in three major coronary arteries, with a threshold of <= 0.8 considered the presence of ischemia. Univariate and multivariate regression was used to evaluate the association of EFV with CAD, palque characteristics, CAC score, Gensini score, and lesion-specific ischemia derived from CT-FFR. Results: Median EFV was 104.97 cm(3) (85.47-136.09) in controls and 129.28 cm(3) (101.19-159.44) in patients (P < 0.001). Logistic regression analysis revealed a significant association of EFV with CAD even after adjusting for confounding factors (P < 0.05). At linear regression analysis, EFV was significantly correlated with high-risk plaque and lesion-specific ischemia, but not with non-calcified plaque, mixed plaque, calcified plaque, CAC score and Gensini score (P >= 0.05). Conclusion: We found that EFV was associated with CAD, suggesting that it may be a promising marker of CAD. EFV was also correlated with high-risk plaque and lesion-specific ischemia, indicating that EAT was likely to be involved in myocardial ischemia and had the potential to definite patients' risk profile. (C) 2021 Elsevier B.V. All rights reserved.