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Percutaneous transcatheter closure has been proposed as an alternative to surgical closure or long-term anticoagulation in patients with presumed paradoxical embolism and patent foramen ovale (PFO). We report our mid-term results of 55 consecutive symptomatic patients (mean age: 47 years, range: 20–79) who underwent percutaneous transcatheter closure of PFO after at least one event of cerebral ischemia; 16 (29%) patients had at least one transient ischemic attack and 39 (71%) patients at least one embolic stroke. Multiple embolic events had occurred in 6 (11%) patients. Percutaneous transcatheter closure was technically successful in all 55 patients (100%). For the majority of patients, an Amplatzer PFO occluder measuring 25 mm in diameter (n = 49) or an Amplatzer PFO occluder measuring 35 mm in diameter (n = 6) was used. Complete occlusion by color Doppler and transesophageal contrast echocardiography investigation was achieved in 96% at follow-up 3-6 months after implantation; only 2 patients had a trivial residual shunt at follow-up. Mean fluoroscopy time was 6.7 minutes (range: 1.7–47.1), and in-hospital follow-up was uneventful except for 1 patient who developed a cardiac tamponade requiring uneventful and successful needle pericardiocentesis. At a mean follow-up of 19 months (range: 3–32) no recurrent embolic neurological events was observed. Transcatheter closure of PFO with Amplatzer PFO occluder devices is a safe and effective therapy for patients with previous paradoxical embolism and aneurysmatic or nonaneurysmatic PFO. Percutaneous closure is associated with a high success rate, low incidence of hospital complications, and freedom of cerebral ischemia events.