Abstract: Objective To evaluate the clinical efficacy of single-operated thoracoscopic cardiopulmonary bypass surgery with beating heart and conventional thoracotomy for atrial septal defect repair. Methods A total of 52 patients with congenital cardiac malformations diagnosed with atrial septal defect from September 2015 to December 2018 in the Cardiac Surgery Center of the First Affiliated Hospital of Bengbu Medical College were divided into observation group(single operation thoracoscopy group, 25 cases) and control group(conventional thoracotomy, 27 cases) according to different surgical methods. The general conditions of patients, extracorporeal circulation time, total operation time and other perioperative indicators, postoperative complications, and postoperative follow-up were analyzed. Results The operations of the two groups were successfully completed. There was no significant difference in the operation time, CPB time, upper and lower cavity block time, and postoperative complications between the two groups(all P>0.05). There were significant difference in postoperative ventilator assist time [(10.80±4.70) h vs.(14.28±6.13) h, t=2.282, P=0.027], ICU time [(28.19±9.15) h vs.(46.54±21.51) h, t=4.053, P<0.001], intraoperative blood transfusion volume [(216.00±172.43) mL vs.(366.67±227.02) mL, t=2.679, P=0.010], 24 hours postoperative drainage [(146.32±157.78) mL vs.(315.37±251.87) mL, t=2.893, P=0.006], and length of hospital stay [(14.84±3.33) d vs.(19.48±7.46) d, t=2.933, P=0.006]. The patients in the two groups were followed up for 2 to 36 months after operation without residual shunts and other abnormalities, and the results were satisfactory. Conclusion The single-hole thoracoscopic atrial septal repair with beating heart is safe, effective and feasible for the treatment of atrial septal defect. The trauma is small, the postoperative recovery is quick, and the incision is more beautiful. It is worthy of popularization and application.