Background: Thrombus formation in the left atrial appendage (LAA) is the main cause of thromboembolic events in patients with non-valvular atrial fibrillation (AF). Oral anticoagulants are considered first-line therapy for stroke prevention in AF patients. Despite its proven efficacy, long-term oral anticoagulation is associated to innumerous limitations. Percutaneous LAA closure has emerged as a new strategy for stroke prevention in high risk AF patients who are not candidates for long term oral anticoagulation therapy. Methods: We report the initial experience with percutaneous occlusion of the LAA using the new Amplatzer TM Cardiac Plug (ACP -AGA Medical Corp., Golden Valley, USA) in patients with AF and CHADS2 score > 2 who were not eligible for anticoagulation therapy. Procedures were carried out under general anesthesia and 3D transesophageal echocardiography monitoring in real time. Results: Three male patients, mean age of 79 years and CHADS2 2, 3 and 5 scores had the device successfully implanted using a transeptal approach with no complications, resulting in immediate LAA occlusion and hospital discharge two days later. At the 50-day followup, all patients were clinically well with complete LAA occlusion and no complications at transthoracic echocardiography. Conclusions: Percutaneous LAA occlusion with the new ACP seems to be an attractive alternative to prevent thromboembolic events in patients with AF and contraindications or limitations for anticoagulation therapy.