We sought to evaluate the effect of weight loss on echocardiographic epicardial fat thickness, as index of visceral adiposity, and whether epicardial fat change after the weight loss can be proportionally different from overall body weight changes and related to cardiac parameters changes in severely obese subjects. This was an interventional study in 20 severely obese subjects (12 women, 8 men, BMI 45+/-5 kg/m(2), 35+/-10 years) who underwent 6-month very low calorie diet weight loss program. Baseline and after 6-month weight loss anthropometrics, echocardiographic epicardial fat thickness, left ventricular mass (LVM), and diastolic function parameters were assessed. Subjects lost 20% of original body weight, BMI reduced by 19% of original BMI, waist circumference decreased by 23% of initial waist circumference. Epicardial fat thickness decreased from 12.3+/-1.8 to 8.3+/-1 mm P<0.001 after the 6-month very low calorie diet, as -32% of baseline epicardial fat thickness. LVM and diastolic function changes were better correlated with epicardial fat changes. We showed that significant weight loss can be associated with significant reduction in the epicardial fat thickness, marker of visceral adiposity in severely obese subjects. Epicardial fat decrease, therefore visceral fat decrease, can be proportionally higher than overall adiposity decrease. Epicardial fat changes are significantly associated with obesity-related cardiac morphological and functional changes during weight loss. Measurement of echocardiographic epicardial fat thickness may provide an additional tool in understanding the metabolic risk associated with variation in fat distribution.