Background In adults with atrial septal defect (ASD) and large right-to-left shunt, closure of the defect is recommended. Percutaneous closure is still rarely used in this population. This study presents the results of transcatheter closure with the Amplatzer occluder in such patients. Methods and Results We studied 44 consecutive adult patients with a secundum ASD and 2 of the 3 following criteria: QP/QS ≥2 by oximetry, echocardiographic right ventricle overload, and ASD size >20 mm. Forty-two patients had a successful implantation. In 1 patient an unstable device was withdrawn; in another one, the device embolized in the pulmonary artery. At 6-month median follow-up, 95% had a complete closure; 2 patients with an additional defect had a small residual shunt. Major complications were the aforementioned embolization and a cerebrovascular accident in a patient with atrial fibrillation treated with aspirin. Others were minor and transitory: premature atrial beats in 3 patients, and paroxysmal atrial fibrillation and pulmonary edema in 1 patient each. Conclusions Transcatheter closure of large ASDs with the Amplatzer device is efficient with less morbidity than surgical closure. (Am Heart J 2001;142:544-8.)