This study examines the safety and efficacy of transthoracic echocardiographic (TTE) guidance of atrial septal defect (ASD) device closure. We evaluated 74 patients for TTE-guided ASD closure. Fifty-six patients had successful device implantation using TTE guidance. Twelve patients were referred for surgical ASD closure on the basis of TTE evaluation. Five patients with multiple ASDs or poor transthoracic acoustic windows had ASD device closure guided by transesophageal echocardiography (TEE).