Purpose: The Energy Balance Study (EBS) was a comprehensive study designed to determine over a period of 12 months the associations of caloric intake and energy expenditure on changes in body weight and composition in a population of healthy men and women. Method: EBS recruited men and women aged 21 to 35 years with a body mass index between 20 and 35 kg/m[superscript 2]. Measurements of energy intake and multiple objective measures of energy expenditure, as well as other physiological, anthropomorphic and psychosocial measurements, were made quarterly. Resting metabolic rate and blood chemistry were measured at baseline, 6 and 12 months. Results: Four hundred and thirty (218 women and 212 men) completed all baseline measurements. There were statistically significant differences by sex uncovered for most anthropomorphic, physiological and behavioral variables. Only percent of kcals from fat and alcohol intake, as well as energy expenditure in light activity and very vigorous activity were not different. Self-reported weight change (mean ± SD) over the previous year were 0.92 ± 5.24 kg for women and -1.32 ± 6.1 kg for men. Resting metabolic rate averages by sex were 2.88 ± 0.35 ml/kg/min for women and 3.05 ± 0.33 ml/kg/min for men. Conclusion: Results from EBS will inform our understanding of the impact of energy balance components as they relate to changes in body weight and composition. Initial findings suggest a satisfactory distribution of weight change to allow for robust statistical analyses. Resting metabolic rates well below the standard estimate suggest that the evaluation of the components of total energy expenditure will be impactful for our understanding of the roles of energy intake and expenditure on changes in energy utilization and storage.