Epicardial adipose tissue (EAT) deposition has been long associated with heart weight. However, recent research has failed to replicate this association. We aimed to determine the association of EAT volume with heart weight in post-mortem cases and identify potential confounding variables. EAT volume derived from post-mortem computed tomography (PMCT) and heart weight were measured in post-mortem cases (N = 87, age: 56 ± 16 years, 28% female). Cases with hypertrophied heart weights (N = 44) were determined from reference tables. Univariable associations were tested using Spearman correlation and simple linear regression. Independence was determined with stepwise regression. In the total cohort, EAT volume (median 66 ± 45 cm3) was positively associated with heart weight (median 435 ± 132 g) at the univariable level (r = 0.6, P < 0.0001) and after adjustment for age, female sex, and various body size metrics (R2 adjusted = 0.41–0.57). Median EAT volume was 1.9-fold greater in cases with hypertrophic hearts (P < 0.0001) but with considerably greater variability, especially in cases with extreme EAT volume or heart weight. As such, EAT volume was not associated with heart weight in hypertrophic cases, while a robust independent association was found in non-hypertrophic cases (R2 adjusted = 0.62–0.86). EAT mass estimated from EAT volume found that EAT comprised approximately 13% of overall heart mass in the total cases. This was significantly greater in cases with hypertrophy (median 15.5%; range, 3.6–36.6%) relative to non-hypertrophied cases (12.5%, 3.3–24.3%) (P = 0.04). EAT volume is independently and positively associated with heart weight in post-mortem cases. Excessive heart weight significantly confounded this association.