Background Although video-assisted thoracoscopic surgery (VATS) lobectomy is widely accepted, VATS pneumonectomy remains an uncommon procedure in patients with complicated diseases. Methods Of 47 consecutive patients who were planned to undergo VATS pneumonectomy from May 2000 to May 2012 at the National Hospital Organization Himeji Medical Center, VATS pneumonectomy was completed successfully in 46 patients (2.1% conversion rate). Appropriate tissue retraction and cooperative dissection of hilum structures under only thoracoscopic visualization were applied to all candidates. We retrospectively reviewed morbidity, mortality, local disease control, and surgical considerations to evaluate the validity of this procedure. Results All patients had malignant tumors, including 45 with primary lung cancer. One patient with a severe adhesion around a tumor required conversion to open thoracotomy, with no subsequent specific complications. Of 46 patients in whom VATS pneumonectomy was completed, the mean operation time was 159 minutes and the mean blood loss was 258 g. Surgery- related death occurred in 1 patient (mortality rate: 2.2%) with recurrent heart failure after discharge. Seven patients (15.2%) had major complications defined as grade 3 or higher (Common Terminology Criteria for Adverse Effects, version 4.0) within 30 days postoperatively; however, no patients exhibited secretion retention that required bronchoscopy. There were no patients with locoregional recurrence within usual lymph node dissection areas and the ipsilateral thoracic cavity among 44 patients with primary lung cancer who underwent VATS pneumonectomy, with the median follow-up time of 27 months. Conclusions Video-assisted thoracoscopic surgery pneumonectomy has developed into a common procedure with acceptable damage and lower morbidity among selected patients with complicated diseases.