Objectives Pulmonary sequestration is a rare congenital malformation of the lungs. This study aims to evaluate the effectiveness of video-assisted thoracic surgery for the treatment of pulmonary sequestration in a larger series compared with posterolateral thoracotomy. Methods The files of 42 patients with pulmonary sequestration treated via video-assisted thoracic surgery (18 cases) and posterolateral thoracotomy (24 cases) between September 2005 and May 2012 from a single institute were retrospectively reviewed. Data were collected regarding the patient demographics, medical history, preoperative investigations, intraoperative findings, and postoperative course. Results All sequestration lung lesions were found in the lower lobes (31 on the left, 11 on the right), with feeding arteries arising from the thoracic aorta (34 cases) and the abdominal aorta (8 cases). Thirty-nine cases of sequestration were intralobar, and only 3 cases were extralobar. All patients achieved successful resection (including 37 lobectomies, 2 pneumonectomies, and 3 resections of the extralobar lesion). In the video-assisted thoracic surgery group, 1 case was converted to thoracotomy because of an injury to the aberrant artery; 1 case had injury to the left lower pulmonary vein and 1 case had injury to the aberrant artery, which were successfully treated without conversion. No significant differences were found between the 2 groups (video-assisted thoracic surgery vs posterolateral thoracotomy) in terms of the duration of operation, blood loss, amount of chest drainage, duration of chest drainage, length of postoperative hospital stay, and complications. Conclusions Video-assisted thoracic surgery resection for pulmonary sequestration is feasible, although it should be performed by an experienced surgeon with awareness of the potential risk of severe vascular injury.