Background: We evaluated the safety and feasibility of intraoperative device closure of atrial septal defect in infants. Methods: From January 2005 to September 2009, we enrolled 32 infants with secundum-type atrial septal defect in our institution. Patients were divided into two groups: 17 patients in group I had intraoperative device closure and 15 in group II had surgical closure. Intraoperative device closure involved a minimal intercostal incision that was performed after full evaluation of the atrial septal defect by transthoracic echocardiography, and insertion of the device through a delivery sheath to occlude the atrial septal defect. Results: The procedure was successful in all patients. In group I, the size of the implanted occluder ranged between 6 and 10 mm (mean 8.5 ± 1.3 mm), and complete closure rates at 24 hours and 3 months were 94.1% and 100%, respectively. In 15 of 17 infants, minor complications occurred; transient arrhythmia (n = 15) and blood transfusion (n = 6). In group II, all patients needed blood transfusions and suffered from various minor complications. Follow-up at 3 to 24 months was obtained in both groups. During follow-up, clinical development and growth improved in all children with failure to thrive. There were no recurrences, thromboses, or device failures. In our comparative studies, group II had significantly longer intensive care unit stay and hospital stay than group I (p < 0.001). The cost of group I was less than group II (19,816.2 ± 946.7 Renminbi (the Chinese currency) vs 25,250 ± 1,370.7 Renminbi, p < 0.001). Conclusions: Intraoperative device closure of atrial septal defect is a safe and feasible technique for infants. It has the advantages of cost savings, better cosmetic results, and less trauma than surgical closure. © 2010 The Society of Thoracic Surgeons.