Objective: The purpose of this study was to evaluate the frequency and risk of postoperative cardiopulmonary and bronchial complications in patients with locally advanced lung cancer after induction chemoradiotherapy and definitive surgery. Methods: We reviewed the charts of 350 patients who underwent thoracotomy in the course of two phase II and one phase III studies with preoperative chemotherapy (three cycles of split- dose cisplatin/etoposide in 261 patients and cisplatin/paclitaxel in 89 patients) followed in all 350 patients by concurrent chemoradiotherapy (one cycle cisplatin/etoposide combined with 45 Gy hyperfractionated accelerated radiotherapy) and operation from March 1991 to December 2000. Univariate and multivariate analysis was used to identify predictors of complications. Results: Of 350 consecutive patients 278 (79%) had a non-small cell lung cancer (154 stage IIIA and 124 IIIB) and 72 (21%) a small cell lung cancer (12 stage IIA/B, 35 stage IIIA and 25 stage IIIB). Resections included 125 pneumonectomies (35%), 15 bilobectomies (4.3%), 37 sleeve lobectomies (11%), 157 lobectomies (45%), and two segmentectomies (0.6%); 14 patients (4%) had an exploration only. Additionally to pulmonary resection 32 patients underwent a partial chest wall resection. One hundred and fifty-four patients (44%) developed early or late complications; the hospital mortality rate was 4.9% (17 patients). The causes of death were sepsis (n=5), pneumonia and respiratory failure (n=4), adult respiratory distress syndrome (n=3), cardiac failure (n=3) and lung embolism (n=2). Multivariate analysis extracted increased age, lower Karnofsky status, abnormal echocardiographic findings and no bronchial stump covering technique to be risk factors for perioperative morbidity. Lower Karnofsky status and increased age were significant risk factors for postoperative mortality. Conclusion: This retrospective analysis demonstrates that in patients with locally advanced lung cancer and induction chemoradiotherapy, surgery can be feasible with acceptable mortality but increased morbidity. Accurate cardiopulmonary evaluation before surgery and standard operative techniques with protection of bronchial stump or anastomosis can contribute to a reduced complication rate with this intensive approach.