OBJECTIVE: The current study was prospectively designed to explore the application of video-assisted thoracoscopic surgery (VATS) radical treatment for patients with stage IIIA lung cancer, with the primary endpoints being the safety and feasibility of this operation and the second endpoints being the survival and complications after the surgery. METHODS: A total of 51 patients with radiologically or mediastinoscopically confirmed stage IIIA lung cancer underwent VATS radical treatment, during which the standard pulmonary lobectomy and mediastinal lymph node dissection were performed after pre-operative assessment. The operative time, intraoperative blood loss/complications, postoperative recovery, postoperative complications, and lymph node dissection were recorded and analyzed. This study was regarded as successful if the surgical success rate reached 90% or higher. RESULTS: A total of 51 patients with non-small cell lung cancer (NSCLC) were enrolled in this study from March 2009 to February 2010. The median post-operative follow-up duration was 50.5 months. Of these 51 patients, 41 (80.4%) had N2 lymph node metastases. All patients underwent the thoracoscopic surgeries, among whom 50 (98%) received pulmonary lobectomy and mediastinal lymph node dissection completely under the thoracoscope, 6 had their incisions extended to about 6 cm due to larger tumor sizes, and 1 had his surgery performed using a 12 cm small incision for handling the adhesions between lymph nodes and blood vessels. No patient was converted to conventional open thoracotomy. No perioperative death was noted. One patient received a second surgery on the second post-operative day due to large drainage (>1,000 mL), and the postoperative recovery was satisfactory. Up to 45 patients (88.2%) did not suffer from any perioperative complication, and 6 (11.8%) experienced one or more complications. CONCLUSIONS: VATS radical treatment is a safe and feasible treatment for stage IIIA lung cancer.