BACKGROUND The relation between variation in interindividual levels of energy expenditure and weight gain remains controversial. OBJECTIVE To determine whether or not components of the energy budget predict weight change, we conducted an international comparative study in 2 cohorts of women from sociocultural environments that give rise to the extremes of obesity prevalence. DESIGN This was a prospective study with energy expenditure measured at baseline and weight measured annually for 3 y. Participants included 149 women from rural Nigeria and 172 African American women. The energy budget was determined by using respiratory gas exchange and doubly labeled water. Main outcomes included total, resting, and activity energy expenditure and physical activity level (ie, total energy expenditure/resting energy expenditure); baseline anthropometric measures; and annual weight change. RESULTS Mean body mass index (in kg/m(2)) was 23 among the Nigerians and 31 among the African Americans; the prevalences of obesity were 7% and 50%, respectively. After adjustment for body size, no differences in mean activity energy expenditure or physical activity level were observed between the 2 cohorts. In addition, in a mixed-effects, random-coefficient model, interindividual variation in activity energy expenditure at baseline was unrelated to the subsequent pattern of weight change. CONCLUSIONS These data suggest that interindividual levels of energy expended during activity do not have a large influence on age-related trends in adiposity. In addition, contrary to expectations, these data suggest that mean activity energy expenditure does not vary substantially between contemporary social groups with low and high prevalences of obesity.