Objectives: To explore the safety and efficacy of total thoracoscopic repair of ventricular septal defects (VSD). We compared clinical outcomes of VSD via a total thoracoscopic approach with those of mini-sternotomy. Methods: We retrospectively reviewed clinical data from patients with VSD from 2012 to January 2019. According to the surgical pattern, they were divided into two groups: the total thoracoscopic surgery group (36 patients, 27 females, aged 29.08 ± 9.52 years), and a mini-sternotomy group (31 patients, 12 females, aged 28.39 ± 8.67 years). Results: There were no deaths in either group. In the thoracoscopic group, cardiopulmonary bypass (CPB) time and aortic cross-clamping (ACC) time were significantly longer than those of the mini-sternotomy group (CPB time: 111.78 ± 23.16 min vs 77.58 ± 37.90 min, respectively, p < 0.001; ACC time: 111.78 ± 23.16 min vs 77.58 ± 37.90 min, respectively, p < 0.001). Tracheal intubation time (6.42 ± 3.85 hours vs 28.55 ± 123.18 hours, p = 0.325), intensive care unit (ICU) stay time (20.47 ± 9.52 hours vs 49.65 ± 163.72 hours, p = 0.330), postoperative hospital stay time (5.11 ± 2.48 days vs 5.90 ± 6.27 days, p = 0.488) and chest drainage (139.86 ± 111.71 ml vs 196.13 ± 147.34 ml, p = 0.081) tended to be lower in the thoracoscopy group, although there was no significant difference. No residual shunt or tricuspid regurgitation was found at follow-up. Conclusions: Total thoracoscopic repair is safe and effective in patients with VSD, with or without tricuspid regurgitation.