Transcatheter closure of atrial septal defects (ASDs) was performed mainly in children and adolescents. Information about outcome and complications in adults was limited. From November 1997 to November 2005, percutaneous closure of ASDs using the Amplatzer septal occluder was attempted in 650 consecutive adult patients. Median patient age was 45.8 ± 16.2 years (range 18 to 90), mean systolic artery pressure was 33.3 ± 10.6 mm Hg (range 11 to 85), and mean pulmonary and systemic blood flow (Qp/Qs) ratio was 1.9 ± 0.7 (range 0.8 to 6.6). Mean stretched diameter of the ASD was 21.2 ± 5.1 mm (range 3.1 to 43). Seventy-eight patients (12%) had multiple defects. Of 572 patients with a single ASD, device implantation was successful in 563 patients (98%). During follow-up, complete closure could be achieved in 96% of patients with a single ASD and 71% of patients with multiple defects. Mean systolic artery pressure decreased to 28.3 ± 10.1 mm Hg and mean Qp/Qs ratio decreased to 1 ± 0.3. The 3 complications that occurred during the procedure were device embolization (2 patients; 0.3%) and transient ST depression (1 patient; 0.2%). The most common complication immediately after the procedure and during follow-up was new-onset atrial fibrillation (28 patients; 4.3%). Electrical cardioversion was successfully in most. Complications requiring emergency or elective surgery occurred in 6 patients (0.9%; hemopericardium, 2 patients, 0.3%; device embolization, 3 patients, 0.5%, and pericardial tamponade, 1 patient, 0.2%). In conclusion, closure of ASDs using the Amplatzer septal occluder in adults was efficient and safe, with excellent long-term success rates. Serious complications were rare.