Background: Patent foramen ovale (PFO) closure is the gold standard for treating patients with cryptogenic stroke and PFO. However, scarce data exist on the long-term outcomes following PFO closure. Objectives: The purpose of this study was to determine the long-term (>10 years) clinical outcomes (death, ischemic, hemorrhagic events) following transcatheter PFO closure. Methods: We included 201 consecutive patients (mean age: 47 ± 12 years, 51% women) who underwent PFO closure due to a cryptogenic embolism (stroke: 76%, transient ischemic attack [TIA]: 32%, systemic embolism: 1%). Echocardiographic examinations were performed at 1- to 6-month follow-up. Ischemic and bleeding events and antithrombotic medication were collected at a median follow-up of 12 years (range 10 to 17 years), and follow-up was complete in 96% of the patients. Results: The PFO closure device was successfully implanted in all cases, and residual shunt was observed in 3.3% of patients at follow-up echocardiography. A total of 13 patients died at follow-up (all from noncardiovascular causes), and nondisabling stroke and TIA occurred in 2 and 6 patients, respectively (0.08 strokes per 100 patient-years; 0.26 TIAs per 100 patient-years). A history of thrombophilia (present in 15% of patients) tended to associate with a higher rate of ischemic events at follow-up (p = 0.067). Bleeding events occurred in 13 patients and were major (intracranial bleeding) in 4 patients (all of them under aspirin therapy at the time of the event). A total of 42 patients stopped the antithrombotic treatment at a median of 6 months (interquartile range 6 to 14 months) post-PFO closure, and none of them had any ischemic or bleeding episode after a mean of 10 ± 4 years following treatment cessation. Conclusions: PFO closure was associated with a low rate of ischemic events (stroke, 1%) at >10 years of follow-up. Major bleeding events occurred in 2% of the patients (all of them in patients on antiplatelet therapy). One-fifth of patients stopped the antithrombotic therapy during the follow-up period (the majority within the first-year post-PFO closure), and this was not associated with any increase in ischemic events at long-term follow-up.