The independent impact of regional and total body composition and sex and thyroid hormone levels on resting energy expenditure (REE) was assessed in 121 healthy, overweight (body mass index [BMI], 25 to 42 kg/m2), postmenopausal women (aged 49 to 58 years). REE was measured by indirect calorimetry with a ventilated hood, and the total, trunk, and peripheral body composition by dual-energy x-ray absorptiometry (DXA). Sex and thyroid hormone levels were also measured. REE correlated significantly (P < .05) better with trunk lean tissue mass ([LTM] r = .61) than with total-body (r = .53) or peripheral LTM (r = .30). Trunk LTM (R2 = .37), total-body fat tissue mass ([FTM] R2 = .04), androstenedione (R2 = .03), and total triiodothyronine ([T3] R2 = .02) were all significantly independently associated with REE. Together they explained 46% (model R2) of the interindividual variation in REE, with a standard error of estimate (SEE) of 549 kJ/d. We conclude that the interindividual variation in REE is explained mainly by differences in the visceral component of LTM, with additional minor information from the total-body FTM, androstenedione, and T3.