The purpose of this study is to compare early clinical outcomes of surgical repair for isolated atrial septal defect (ASD) with a totally thoracoscopic approach without robotic assistance versus a conventional open procedure.Between September 2010 and June 2012, 254 consecutive patients with isolated ASD underwent totally thoracoscopic surgery without robotic assistance in seven institutions participating in the nationwide multi-centered registry in China. During the same period, these patients were matched using propensity score methodology with 254 patients who had accepted conventional open surgery through a median sternotomy. The early in-hospital results between the two groups were analyzed and compared.The patient age was 26.8 ± 14.0 years and weight was 52.9 ± 16.9 kg in the totally thoracoscopic group. The totally thoracoscopic surgery required longer aortic clamp time (32.1 ± 17.3 minutes versus 28.3 ± 16.7 minutes, P = .01); shorter length of stay in the intensive care unit (25.3 ± 12.2 hours versus 34.8 ± 24.4 hours, P = .001); shorter length of stay in hospital (6.5 ± 6.3 days versus 7.9 ± 6.4 days, P = .008); and shorter mechanical ventilation time (8.3 ± 5.0 hours versus 11.4 ± 14.8 hours, P = .04). The cardiopulmonary bypass (CPB) time (62.7 ± 29.3 minutes versus 61.5 ± 28.0 minutes, P = .64) showed no significant difference between the two groups. The totally thoracoscopic group had significantly less postoperative chest tube drainage (322.1 ± 213.7 mL versus 462.8 ± 398.4 mL, P = .001). The intraoperative (35.4% versus 38.6%, P = .46) and postoperative blood products usage (20.9% versus 21.3%, P = .91) showed no significant difference between the two groups.There also was no significant difference in mortality and major in-hospital complications between the two groups. The early outcomes for treatment of isolated ASD were similar between the totally thoracoscopic group conventional open operation performed through median sternotomy, despite a longer aortic clamp time in the totally thoracoscopic group.