Objective To analyze the clinical efficacy of totally thoracoscopic surgery and conventional thoracotomy in repair of ventricular septal defect (VSD). Methods We retrospectively reviewed the clinical data of 50 VSD patients admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2015 to January 2017. According to the surgical pattern, they were divided into two groups: a totally thoracoscopic surgery group (21 patients, 13 males, 8 females, aged 38.36±10.02 years), and a thoracotomy group (29 patients, 18 males, 11 females, aged 42.36±13.02 years). The operation time, hospital stay, ventilator-assisted time and thoracic drainage were compared between the two groups. Results There was no death in two groups. In the thoracoscopic group the duration of cardiopulmonary bypass (CPB) time and the aortic clamping time were longer than those of the thoracotomy group (P<0.05), but postoperative drainage, patients with postoperative use of blood products and postoperative hospital stay were less (P<0.05). There was no statistically significant difference between the two groups in operation time, postoperative ventilator-assisted time or duration of ICU stay. Conclusion Compared with the conventional thoracotomy, totally thoracoscopic VSD repair with less trauma, quicker recovery and less blood use, is safe and reliable and can be used as a preferred surgical intervention.