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Objective To evaluate the safety and feasibility of transcatheter closure of large secundum atrial septal defects (ASDs) with Amplatzer septal occluder (ASO). Methods A total of 26 patients (age 16 to 67 years, median 43 years; body weight 52 to 102 kg, median 67 kg) with large ASDs underwent an attempted transcatheter closure using ASO. Large ASD was defined as those with a balloon-stretched diameter of ≥30 mm. Another 81 patients with small-to-moderate ASD during same period who underwent closure served as controls.Results In patients with large ASDs, the ASD dimension means were (22.1±3.2) mm (range from 16 to 30 mm) and (23.8±2.6) mm (range from 18 to 31mm) assessed by transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE), respectively. The mean balloon-stretched diameter of the ASD was (31.9±2.1) mm (range from 30 to 37mm). The size of device was (32.0±1.9) mm (range from 30 to 36mm). The transcatheter procedure was successful in all patients (100%). Seventeen deployments were performed using the conventional left atrium approach, and remaining 9 patients required the right upper pulmonary vein approach. Immediately after deployment, TEE revealed that complete closure rate was 73%. Procedure-related complications were recorded in 3 patients (12%), including device embolization in one patient, pericardial effusion in one patient, and large hematoma at puncture site in one patient. During follow-up, the complete closure rate increased to 88% at 24h after procedure and 100% at 6 months. The procedural success rates, immediate TEE results and TTE results at 24h and 6 months after procedure, were not significantly different between patients with large ASDs and those with small-to-moderate ASDs. Conclusion Transcatheter closure of large ASDs using ASO is technical feasible and relatively safe. Proper care selection and specific technique modification such as the right upper pulmonary vein approach is vital for the implantation success.