Percutaneous closure of atrial septal defects (ASD) is increasingly performed in pediatric and adult patients. This study reports a single-center experience with the use of the Amplatzer Septal Occluder for percutaneous ASD closure in adults. One hundred and seventeen consecutive patients were prospectively included in the database. The procedure was successful in 106 patients (90.6%). The mean age was 50 years. Eighty-four percent of the patients had a Qp:Qs > 1.5. Other indications included a history of thromboembolism, decreased exercise tolerance, atrial arrhythmias, evidence of pulmonary hypertension or right heart overload. Mean procedure time was 44 minutes, and mean fluoroscopy time was 13 minutes. The mean defect diameter was 17.2 mm (range, 5 30 mm). There was no residual shunting at the end of the procedure in 75% of the patients. Shunting was minimal in all but 2 of the remaining 25 patients (1.8%). No major complications were observed at a mean follow-up of 19 months. Patients in whom the procedure failed had larger defects (mean, 25.0 mm versus 18.3 mm; p < 0.001), larger right ventricles (44.1 mm versus 38.2 mm; p = 0.03) and more significant shunting (Qp:Qs, 3.5 versus 2.1; p < 0.001). New York Heart Association functional class improved in all but 1 patient. Percutaneous ASD closure using ASO is safe and mid-term results compare favorably with those reported with surgical ASD closure. It can therefore be recommended as the first line of treatment in adult patients with secundum ASD.