Background: Neoadjuvant chemotherapy or chemoradiotherapy increases the risk of pulmonary resection. Changes in specific pulmonary function tests may be predictive. Methods: A retrospective review of a prospective database of patients with non-small cell lung cancer who underwent neoadjuvant therapy, had pulmonary function tests performed both before and after therapy, and then underwent elective pulmonary resection was performed. Final values and change in the pulmonary function tests before and after treatment were entered as independent variables into a multivariate model in which the dependent variable was major or respiratory morbidity. Results: There were 132 patients. The mean duration between pretherapy and posttherapy pulmonary function tests was 4.1 months. The mean change in the percent forced expiratory volume in 1 second, in the percent diffusion capacity of the lung for carbon monoxide, and in the percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume was +1.0, -6.4%, and -6.6%, respectively. Fifty-five patients (42%) experienced a postoperative complication, and 39 of those patients experienced a major or respiratory complication. There were 7 (5.3%) operative mortalities (5 were respiratory related). On multivariate analysis the change in the percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume was the only factor associated with major or respiratory morbidity (p = 0.028). When the posttherapy percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume fell by 8% or more, there was an increased likelihood of major morbidity (p = 0.01). Conclusions: A decrease in the percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume after neoadjuvant chemotherapy or chemoradiotherapy may predict increased risk for pulmonary resection, especially if the decrease is 8% or greater. These results should be considered in the preoperative risk assessment of patients who are to undergo pulmonary resection after induction therapy. © 2009 The Society of Thoracic Surgeons.