Objective To compare surgical results between real-time three dimensional echocardiography（RT-3DE） guided closure of atrial septal defect （ASD） through a right minithoracotomy and traditional surgical repair under cardiopulmonary bypass （CPB）. Methods Sixty-four patients with secundum ASD received surgical repair in the First People’s Hospital of Honghe Autonomous Prefecture from April 2009 to April 2012. According to different surgical approach, all the patients were divided into group A and B. In group A, 35 patients underwent traditional ASD repair under CPB including 20males and 15 females with their age of 12-56 （16.4±4.0） years. In group B, 29 patients received real-time RT-3DE guidedASD closure through a right minithoracotomy without CPB, including 20 males and 15 females with their age of 15-50 （18.5±0.2） years. Operation time，postoperative mechanical ventilation time，hospital stay，chest drainage，mortality，morbidity and follow-up outcomes were compared between the 2 groups. Results Operation time （110.47±35.90 minutesvs. 159.32±20.60 minutes），postoperative mechanical ventilation time （10.40±22.30 hours vs. 16.40±12.20 hours），chestdrainage （106.71±85.20 ml vs. 146.70±75.63 ml）and postoperative hospital stay （4.0±1.0 days vs. 7.0±1.0 days）ofgroup B were significantly shorter or less than those of group A. In group A, 1 patient died postoperatively and 7 patientshad postoperative complications. In group B, there was no in-hospital mortality and 3 patients had postoperative complications.Postoperative morbidity of group A was significantly higher than that of group B （20.0% vs. 10.3%，P＜0.05） . ConclusionFor ASD patients with definite surgical indications，RT-3DE guided ASD closure through a right minithoracotomy has more advantages over traditional surgical repair under CBP.