Objective To analyze the safety and effectiveness of ultrasound-guided thoracoscopic atrial septal defect (ASD) closure. Methods We prospectively collected the clinical data of 12 patients with ASD treated by ultrasound-guided thoracoscopic ASD closure in Fuwai Hospital from January to September 2017. The characteristics of the patients' ASD and operation, operation safety and effectiveness, postoperative complications and follow-up results were analyzed. Results Among the 12 patients, 10 were successfully treated with ultrasound-guided thoracoscopic ASD closure. Two patients switched to ASD repair under thoracoscopy-assisted cardiopulmonary bypass. The size of the ASD was 17-40 (27.22±8.97) mm and the size of the occluder was 36 (30-42) mm. The average postoperative length of hospital stay was 6 days. There were no complications such as arrhythmia, bleeding and pericardial effusion after operation. The average follow-up was 6 (3-10) months after the operation. During the follow-up, no Ⅲ-degree conduction block, occluder dislocation, residual shunt or cardiac pericardial effusion was found. Conclusion Ultrasound-guided thoracoscopic ASD closure is a minimally invasive, safe and effective treatment. This technique provides a new minimally invasive surgical option for patients with large defect diameter and poor edge condition.