Background: Although physical inactivity is believed to contribute to the rising prevalence of obesity, the role and magnitude of its contribution to weight gain are unknown. Objective: We compared total free-living activity energy expenditure (AEE) and physical activity level in women successful and unsuccessful at maintaining a normal body weight. Design: Premenopausal, generally sedentary women were studied at their normal weight and 1 y later after no intervention. Two groups were identified on the basis of extreme weight changes: maintainers (n = 27) had a weight gain of ≤ 3% of their initial body weight (≤ 2 kg/y) and gainers (n = 20) had a weight gain of > 10% (>6 kg/y). At baseline and follow-up, evaluations were conducted during 4 wk of diet-controlled, energy-balance conditions. Free-living AEE and physical activity were assessed with the use of doubly labeled water, exercise energy economy and muscle strength with the use of standardized exercise tests, and sleeping EE and substrate utilization with the use of chamber calorimetry. Results: Maintainers lost a mean (±SD) of 0.5 ± 2.2 kg/y and gainers gained 9.5 ± 2.1 kg/y. Gainers had a lower AEE (P < 0.02), a lower physical activity level (P < 0.01), and less muscle strength (P < 0.001); these differences between groups remained significant from baseline to follow-up. Sleeping EE, exercise economy, and sleeping or 24-h substrate utilization were not significantly different between the 2 groups. A lower AEE in the gainers explained ≅77% of their greater weight gain after 1 y. Conclusion: The general US population should increase their daily physical activity levels to decrease the rising prevalence of obesity.