Objective: To assess the feasibility and safety of the video-assisted thoracoscopy surgery (VATS) systematic lymph node dissection in resectable non-small cell lung cancer (NSCLC). Methods: The clinical data of patients with NSCLC who underwent VATS or thoracotomy combined with lobectomy and systematic lymphadenectomy from January 2001 to January 2008 were retrospectively analyzed to identify their demographic parameters, number of dissected lymph nodes and postoperative complications. Results: A total of 5,620 patients were enrolled in this study, with 2,703 in the VATS group, including 1,742 men (64.4%), and 961 women (35.6%), aged 59.5 +/- 10.9 years; and 2,917 in the thoracotomy group, including 2,163 men (74.2%), and 754 women (25.8%), aged 58.5 +/- 10.4 years. Comparing the VATS with the thoracotomy groups, the mean operative time was 146 vs. 157 min, with a significant difference (P<0.001); and the average blood loss was 162 vs. 267 mL, with a significant difference (P<0.001). Comparing the two groups of patients data, the number of lymph node dissection: 18.03 in the VATS group and 15.07 in the thoracotomy group on average, with a significant difference (P<0.001); postoperative drainage time: 4.5 days in the VATS group and 6.37 days in the thoracotomy group on average, with a significant difference (P<0.001); postoperative hospital stay: 6.5 days in the VATS group and 8.37 days in the thoracotomy group on average, with a significant difference (P<0.001); proportion of postoperative chylothorax: 0.2% (4/2,579) in the VATS group and 0.4% (10/2,799) in the thoracotomy group, without significant difference (P>0.05). Conclusions: For patients with resectable NSCLC, VATS systematic lymph node dissection is safe and effective with fewer postoperative complications, and significantly faster postoperative recovery compared with traditional open chest surgery.