Both unilateral and bilateral lung volume reduction procedures are being advocated for treatment of severe, generalized emphysema. We analyzed the results of 166 consecutive patients who underwent unilateral (n = 87) or bilateral (n = 79) thoracoscopic stapled lung volume reductions to help define the role for these procedures. There was no statistically significant difference in the operative mortality (3.5% vs 2.5%), mean length of stay (11.4 +/- 1 vs 10.9 +/- 1 days), or morbidity for the unilateral and bilateral groups, respectively (p not significant for all variables). Oxygen dependence was eliminated in 18 (36%) of 50 patients who had unilateral procedures and 30 (68%) of 44 of those who had bilateral procedures (p < 0.01). Prednisone was eliminated for 38 (54%) of 51 unilateral-procedure patients, compared with 30 (85%) of 35 bilateral-procedure patients (p = 0.02). Overall, bilateral procedures produced a mean improvement in the forced expiratory volume in 1 second (FEV1) of 57%, compared with 31% for unilateral reduction procedures (p < 0.01). Our bilateral staple procedure produced a 72.8% mean increase in the FEV1 for patients who had upper lobe emphysema. Especially compromised patients (age > or = 75, with preoperative room air Po2 < or = 50 mm Hg or FEV1 < or = 500 ml) had the same morbidity and operative mortality with unilateral or bilateral procedures, but they had a higher 1-year mortality (17% vs 5%), primarily because of respiratory failure after the unilateral operation (p < .001). Although unilateral staple lung volume reduction may produce an excellent result in a given patient, the bilateral procedure appears to be the procedure of choice, because it provides better overall results at no increased morbidity or mortality compared with the unilateral procedure. The results of bilateral staple lung volume reduction by thoracoscopy appear to be comparable to those of median sternotomy.