Objective To summarize the perioperative nursing experience of transesophageal echocardiography (TEE) guided percutaneous interventional occlusion of atrial septal defect (ASD). Methods 26 cases of patients with ASD who were treated with TEE-guided percutaneous interventional occlusion from November 2015 to April 2017 were selected. The nursing operation specification was developed from the three aspects of intraoperative TEE operation nursing, aseptic operation coordination of surgical closure device and intraoperative related complications indexes observation, and the specification was strictly enforced during operation, and the nursing effects were summarized and analyzed. Results During TEE operation, 1 patient developed oropharyngeal mucosal edema without damage and bleeding, and there was no teeth loosening among patients. There was no contamination of guide wire during operation. Intraoperative monitoring revealed that 1 patient was with frequent atrial premature beats during the procedure of guide wire transportation, and the patient restored normal heart rhythm after adjusting the direction of guide wire with the surgeon. Conclusion Focusing on TEE operation nursing, aseptic operation coordination of surgical closure device and observation of intraoperative related complications indexes can assist TEE-guided percutaneous interventional occlusion for ASD, and reduce the occurrence of surgical complications.