['The relevance of the contribution of energy expenditure (EE) and substrate oxidation to weight change has not been fully confirmed.', 'The objective of the study was to determine whether metabolic parameters measured in a whole room indirect calorimeter are predictive of long-term body weight change.', 'The study was conducted at a clinical research unit in Phoenix, Arizona, from 1985 to 2005.', 'A total of 612 healthy subjects (384 males and 228 females; aged 29.5 ± 8.1 years; body mass index 33.0 ± 8.7 kg/m(2); percent body fat 30.9 ± 9.6%), including 422 Native Americans and 190 whites. Follow-up data were available for 292 Native Americans with a median follow-up time of 6.7 years (interquartile range 3.9-10.5).', 'Twenty-four-hour EE, sleeping metabolic rate, daily (fed) and sleeping (fasting) respiratory quotient, and carbohydrate and fat oxidation rates were measured during a 24-hour respiratory chamber. Body composition was assessed by underwater weighing or dual-energy x-ray absorptiometry.', 'After accounting for demographic and body composition measures, the remaining variance of 24-hour EE was inversely related to the rate of weight change (ρ = -0.158, P = .007) and fat mass change (ρ = -0.179, P = .012), such that 100 kcal below the expected 24-hour EE corresponded to 0.2 kg/y weight gain, of which 0.1 kg/y was fat mass. Deviations from the predicted values of the sleeping metabolic rate (ρ = -0.121, P = .039) and fed respiratory quotient (ρ = 0.119, P = .042) were also associated with future weight change, whereas the fat oxidation rate was inversely associated with weight change in men (ρ = -0.174, P = .024) but not in women (ρ = 0.018, P = .853).'] Does lower energy expenditure predict long-term increases in weight and fat mass?