Rationale: Lung volume reduction surgery (LVRS) is associated with weight gain in some patients, but the group that gains weight after LVRS and the mechanisms underlying this phenomenon have not been well characterized. Objectives: To describe the weight change profiles of LVRS patients enrolled in the National Emphysema Treatment Trial (NETT) and to correlate alterations in lung physiological parameters with changes in weight. . We compared BMI groups and LVRS and medical groups within each BMI stratum with respect to baseline characteristics and percent change in BMI (%DBMI) from baseline. We examined patients with (DBMI > 5%) and without (DBMI , 5%) significant weight gain at 6 months and assessed changes in lung function and ventilatory efficiency (V E/V CO 2 ). Measurements and Main Results: The percent change in BMI was greater in the LVRS arm than in the medical arm in the underweight and normal weight groups at all follow-up time points, and at 12 and 24 months in the overweight group. In the LVRS group, patients with DBMI > 5% at 6 months had greater improvements in FEV 1 (11.53 6 9.31 vs. 6.58 6 8.68%; P , 0.0001), FVC (17.51 6 15.20 vs. 7.55 6 14.88%; P , 0.0001), residual volume (-66.20 6 40.26 vs. -47.06 6 39.87%; P , 0.0001), 6-minute walk distance (38.70 6 69.57 vs. 7.57 6 73.37 m; P , 0.0001), maximal expiratory pressures (12.73 6 49.08 vs. 3.54 6 32.22; P ¼ 0.0205), and V E/V CO 2 (-1.58 6 6.20 vs. 0.22 6 8.20; P ¼ 0.0306) at 6 months than patients with DBMI , 5% at 6 months. Conclusions: LVRS leads to weight gain in nonobese patients, which is associated with improvement in lung function, exercise capacity, respiratory muscle strength, and ventilatory efficiency. These physiological changes may be partially responsible for weight gain in patients who undergo LVRS.