Objective: To investigate the effect of high-altitude exposure (above altitude of 2 000 meters) on safety of c-VATS (complete video-assisted thoracoscopic surgery) lobectomy in elderly patients (> 60 years) with NSCLC (non-small cell lung cancer) and analysis of prognosis. Methods: Matched case-control study was performed to recruit 49 elderly NSCLC patients receiving c-VATS lobectomy and 49 matched (according to clinical staging and histology) elderly NSCLC patients receiving COT (conventional open thoracotomy) lobectomy in high-altitude area between January 1, 2010 and December 31, 2010. The perioperative variables including operative time, intraoperative blood loss, duration of postoperative chest tube placement, postoperative pleural effusion, time to suture removal, length of hospitalization, postoperative incisional pain rating and complication rate were compared between c-VATS lobectomy group and COT lobectomy group. The variables of pulmonary function and arterial blood gas tests before and six months after operation were also compared between the two groups. The follow-up was conducted. The one- and two-year survival rates were calculated and compared between the two groups. Results: The operative time was longer in c-VATS lobectomy group than in COT lobectomy group (P < 0.01). The intraoperative blood loss, duration of postoperative chest tube placement, postoperative pleural effusion, time to suture removal, length of postoperative hospitalization and postoperative incisional pain rating were lower in c-VATS lobectomy group than in COT lobectomy group (P < 0.01). The percentage decrease of VC (vital capacity), FEV (forced vital capacity), FEV1 (forced expiratory volume in one second), FEV1/FEV ratio, FEF25 (forced expiratory flow at 25% of vital capacity), FEF50 and MVV (maximal voluntary ventilation) six months after operation vs before operation was significantly less in c-VATS lobectomy group than in COT lobectomy group (P < 0.05). The percentage increase of PaO2 (arterial partial pressure of oxygen) and PaCO 2 (arterial partial pressure of carbon dioxide) and the percentage decrease of PaC02 (partial pressure of arterial carbon dioxide) six months after operation vs before operation were higher in c-VATS lobectomy group than in COT lobectomy group (P < 0.05). The perioperative complication rates in c-VATS lobectomy group and COT lobectomy group were 4.08% and 12.24%, respectively (P < 0.05). There were no significant differences in one- and two-year survival rates of stages I, II and IIIA patients between c-VATS lobectomy group and COT lobectomy group (P > 0.05). Conclusion: Compared with COT lobectomy, elderly NSCLC patients who undergo c-VATS lobectomy may have less trauma, bleeding and damage of pulmonary function, fewer complications, and more rapid recovery. These results reveal a clinical significance of application of c-VATS lobectomy in high-altitude area. Copyright © 2013 by TUMOR.