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Background: Left Atrial Appendage (LAA) is the main source of left atrial thrombi causing embolic strokes in patients with Non Valvular Atrial Fibrillation (NVAF). Since many patients carry contraindications to Oral Anticoagulation (OAC), percutaneous devices for closure of LAA have been introduced, to avoid peripheral thromboembolism in absence of OAC. Methods: From March 2012 to March 2014 we enrolled patients which had permanent and persistent NVAF and high thromboembolic risk with absolute contraindication to OAC. They were subjected to insertion of Boston Scientific Watchman device in LAA under transesophageal and fluoroscopic guide, with continuous heparin administration to maintain constant activated clotting time (ACT) of 300-350 sec and under general anesthesia. Patients were discharged with indication to double antiplatelet therapy with Aspirin and Clopidogrel for 6 months and Aspirin thereafter, avoiding Warfarin at all. Follow-up Transesophageal Echocardiography (TEE) was performed 2 months, six months and 12 months after implantation. Results: We enrolled 21 patients, aging 49 to 80 yrs. (mean 67.61± 8.2), with high thromboembolic risk (CHADsVasc 3.23 ± 1.33), and with different contraindications to OAC, in most cases due to severe bleeding risk and difficulty in keeping stable INR values (HASBLED 3 ± 1.09). The mean size of the device implanted was 24.75 ± 2.56 mm, the mean total procedure time was 67.78 ± 18 min, the mean fluoroscopy time was 16.81 ± 2.53 min. In all cases LAA was successfully occluded at first TEE, performed within 2 months from the procedure, while we noticed a trend towards development of non-pathological leaks in the next control TEEs, with patients always free from embolic events at mean follow-up of 13.09 ± 6.04 months. Moreover, we noticed a trend towards reduction of left atrial spontaneous echo contrast after LAA closure. Conclusion: Percutaneous LAA closure followed by administration of DAPT appears to be safe and effective at mid-term follow-up in patients with absolute contraindications to OAC. Long term safety and efficacy will be demonstrated with longer follow-up and with more patients enrolled.