Lung resection remains the most effective treatment for non-small cell lung cancer (NSCLC). However, there is no consensus about reliable operative risk assessment in these patients. The aim of this study was to identify predictors of postoperative complications and death after lung resection for NSCLC. In this prospective trial, 125 of 142 (88%) consecutive NSCLC patients from 1990 to August 1997 had complete data sets. All underwent functional assessment including spirometry and cardiopulmonary exercise tests and lung resection via thoracotomy. Complications occurred in 31 of 125 (25%) patients including 2 (1.6%) deaths. On logistic regression analysis, only maximal oxygen uptake (V'O2,max) x kg body weight(-1) expressed as a percentage of the predicted value (p<0.0001) and the estimated extent of lung tissue resection (p=0.02) were independent predictors of postoperative complications. Six of seven patients with a V'O2,max x kg body weight(-1) of <60% pred, but only eight of 65 with values >90% pred, exhibited postoperative complications. Maximal oxygen uptake and the estimated extent of lung tissue resection are independent predictors of postoperative complications. These simple parameters should be integrated into the preoperative decision analysis for operability in patients undergoing lung resection for lung cancer.