Objectives: Patients undergoing pneumonectomy for lung cancer are thought to be at high risk for the development of postoperative pulmonary complications (PC) and these complications are associated with high mortality rates. The purpose of this study was to identify independent factors associated with increased risk for the development of postoperative PC after pneumonectomy for lung cancer, and to assess the usefulness of predicted pulmonary function to identify high risk patients and other adverse outcomes. Patients and methods: We reviewed retrospectively 242 patients undergoing pneumonectomy for lung cancer during a 12-year period. Perioperative data (clinical, pulmonary function test, and surgical) were recorded to identify risk factors of PC by univariate and multivariate analyses. Results: Overall mortality and morbidity rates were 5.4 and 59%, respectively. Thirty-four patients (14%) developed PC (acute respiratory failure, ARF=8.7%, REINTUBATION=5.4%, PNEUMONIA=3.3%, ATELECTASIS=2.9%, postpneumonectomy pulmonary EDEMA=2.5%, mechanical ventilation more than 24 h=1.2%, PNEUMOTHORAX=0.8%). Patients with surgical (P<0.001), cardiac (P<0.001) and other complications (P<0.01) had higher incidence of PC than those without postoperative complications. Intensive care unit stay (53±39 h vs. 35±19 h; P<0.001) and hospital stay (18±11 days vs. 12±7 days; P<0.001) was significantly longer in patients with PC. The mortality rate associated with PC was 35.5% (P<0.001). By univariate analysis, it was found that older patients (P=0.007), chronic obstructive pulmonary disease (COPD) (P=0.023), heart disease (P=0.019), no previous record of chest physiotherapy (P=0.008), poor predicted postoperative forced expiratory volume in 1 s (ppo-FEV1) (P=0.001), and prolonged anesthetic time (P<0.001) were related with higher risk of PC. In the multiple logistic regression model, the anesthetic time (minutes; odds ratio, OR=1.012), ppo-FEV1 (ml/s; OR=0.998), heart disease (OR=2.703), no previous record of previous chest physiotherapy (OR=2.639), and COPD (OR=2.277) were independent risk factors of PC. Conclusions: PC after pneumonectomy are associated with high mortality rates. Careful attention must be paid to patients with COPD and heart disease. Our results confirm the relevance of previous chest physiotherapy and the importance of the length of the surgical procedure to minimize the incidence of PC. The predicted pulmonary function (ppo-FEV1) may be useful to identify high risk patients for PC development and adverse outcomes.