Percutaneous patent foramen ovale (PFO) closure is a treatment for cryptogenic stroke and migraine headache. The goal of this study was to assess long-term outcomes of patients treated with percutaneous PFO closure. Records of patients with percutaneous PFO closure at Emory University Hospital from February 2002 to July 2009 were reviewed. Follow-up telephone questionnaire and chart review assessed recurrent stroke, migraine, and complications. Data was reviewed on 414 consecutive patients. Long-term follow-up was obtained in 207 of patients, and mean follow up was 4.6 ± 2.0 years. Cryptogenic stroke was the primary indication for intervention in 193 (93%) patients. Thirteen (7%) patients had a recurrent neurologic event post closure. In patients with multiple neurological events at baseline, 17% (n = 11) had a recurrent event, compared with 2% (n = 2) of patients with a single neurological event prior to PFO-closure (P < 0.002). Post closure, migraine frequency and severity declined from 4.5 to 1.1 migraine/month (P < 0.01) and 7.2 to 3.6 out of 10 (P < 0.01) in patients with history of migraine (n = 60). Thirty-day mortality was 1% (n = 2). One patient had device erosion 5 years post-procedure requiring emergent surgery. Atrial fibrillation was newly diagnosed in 8 (4%) patients within 6 months. In conclusion, the long-term rate of recurrent stroke after PFO closure is low in patients with a single neurological event at baseline. Serious long-term complications after PFO closure are rare. PFO closure may decrease the frequency and severity of migraine.