Cardiac adiposity defined as increased epicardial adipose tissue and massive deposits of fat within the atrial septum (lipomatous hypertrophy) is seen in overweight persons and is associated with coronary artery disease (CAD), atrial arrhythmias, and increased risk of left ventricular free wall rupture after acute myocardial infarction. Unlike subcutaneous fat, epicardial fat is metabollically active and produces hormones, cytokines, and other vasoactive substances that work systemically or locally to alter vascular endothelial function and may be implicated in the pathogenesis of CAD. The aim of the study was to assess the feasibility of measuring epicardial fat volume (EFV) and identify its clinical correlates using (64-slice) multislice computed tomography (MSCT). A protocol was devised to measure EFV using MSCT in 151 adults (age 26 to 83 years, mean 51 ± 12; 55% men). Cross-sectional tomographic cardiac slices (2.5-mm thick) from base to apex (range 28 to 40 per heart) were traced semiautomatically using an off-line workstation, and EFV was measured by assigning Hounsfield units ranging from −30 to −250 to fat. Coronary computed tomographic angiography was performed using a standard protocol. EFV ranged from 25 to 274 ml (mean 121 ± 47), corresponding to 2.4% to 30.5% (mean 15 ± 5%) of total cardiac volume and correlated with age, atrial septum thickness, body weight, and body mass index. Coronary calcium score was significantly higher in patients with EFV >100 ml (67 ± 155 vs 216 ± 639; p = 0.03), and a higher percentage of patients with increased EFV had CAD (46% vs 31%; p <0.05) or metabolic syndrome (44% vs 29%; p <0.05). In conclusion, quantification of EFV was feasible using MSCT. Large deposits of fat around the heart and within the atrial septum were associated with obesity, coronary calcium, metabolic syndrome, and CAD. Measurement of EFV may provide another useful noninvasive indicator of heightened risk of CAD in addition to calcium score and coronary angiography.