Objectives: Diaphragmatic infiltration by non-small-cell lung cancer (NSCLC) is a rare occurrence and surgical results are unclear. We assessed our experience with en bloc resection of lung cancer invading the diaphragm, analysing prognostic factors and long-term outcomes., Methods: We analysed a prospective database of patients with NSCLC infiltrating the diaphragm who underwent en bloc resection. Univariate analysis was performed to identify prognostic factors. Survival was calculated by the Kaplan-Meier method., Results: Nineteen patients (14 men, mean age 64 ± 11 years) were identified. Surgery included nine pneumonectomies, eight lobectomies and two segmentectomies. A partial diaphragmatic infiltration was observed in 10 patients (53%) and full-depth invasion in 9 (47%). Diaphragmatic reconstruction was done primarily in 13 patients (68%), and by prosthetic material in 6 (32%). Pathological nodal status included nine N0, four N1 and six N2. The median hospital stay was 7 days (range, 4-36 days). The postoperative mortality rate was 5% (1/19). Two patients (10%) had major complications (acute respiratory distress syndrome and bleeding) and 10 minor complications, arrhythmia in 7 (37%) and pneumonia in 3 (16%). The 5-year survival was 30 ± 11%. The median survival and disease-free survival were 15 ± 9 months (range, 1-164 months) and 9 ± 7 months (range, 1-83 months), respectively. Factors adversely affecting survival were diaphragmatic infiltration (50% superficial vs 0% full-depth infiltration; log-rank test, P = 0.04) and nodal involvement (43% N0 vs 20% N1-2; log-rank test, P = 0.03)., Conclusions: Resection of NSCLC invading the diaphragm is technically feasible and could be a valid therapeutic option with acceptable morbidity and mortality and long-term survival in highly selected patients., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)