Background: Percutaneous transcatheter closure of patent foramen ovale (PFO) and atrial septal defect (ASD) has been shown to be feasible. Aim: The aim of this study was to evaluate the safety and efficacy of transcatheter interatrial septal shunt closure with prosthesis implantation in adults patients during long-term follow-up. In addition, the impact of thrombophilia and pulmonary hypertension on the outcome were investigated. Methods: Between June 1999 and November 2009, 287 patients (112 males, 43 ± 14 years) were treated in our institution by transcatheter closure of PFO (N = 175) or ASD (N = 112). Clinical and echocardiographic follow-up were prospectively performed at 1, 6 and 12 months followed by a 1 once a year evaluation. Results: All procedures were successful with eight procedural complications (2.7%): one stroke, two femoral pseudoaneurysms, three transient atrial fibrillation, two minors pericardial effusions. Among patients with presumed paradoxical embolism, thrombophilia was observed in 29 patients (17%); only one of them experienced a recurrent stroke. Among patients with ASD, pulmonary hypertension was observed in 32 cases (28%) and significantly reduced 6 months after shunt closure (from 47 ± 7 to 31 ± 11 mm Hg, P < 0.0001). 99% of patients achieved a complete follow-up. Clinical improvement was observed in 93%. Freedom from death, cardiac surgery or recurrent embolism was 98 ± 1% at 5 years. Conclusion: Percutaneous transcatheter interatrial septal defect closure is a safe and effective treatment in adults patients, even in case of thrombophilia or pulmonary hypertension, during a long-term follow-up, up to 11 years. © 2011 Wiley Periodicals, Inc.