A retrospective study was conducted on 171 patients undergoing coronary CT to evaluate the feasibility of region-of-interest (ROI)-based measurements of epicardial fat density (EFD) as an alternative to global volumetric EFD segmentation. Regional EFD was assessed by manually placing three predefined ROIs—at the aortic bulb, right posterolateral wall, and cardiac apex—on nonenhanced scans acquired for coronary calcium scoring. Global EFD was calculated using semiautomated segmentation. A statistically significant correlation was observed between regional and global EFD values (p < 0.0001). The results demonstrate notable regional variability in EFD across specific cardiac areas, suggesting that ROI-based assessments may not reliably reflect global EFD characteristics.