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Background--Patients with ischemic stroke or transient ischemic attack presumably related to patent foramen ovale (PFO) are at risk for recurrent cerebrovascular events. Differences in long-term clinical outcome were investigated among patients with percutaneous PFO closure and those who received medical treatment. Methods and Results--Between 1994 and 2000, 308 consecutive patients with cerebrovascular events presumably related to PFO underwent either percutaneous PFO closure (150 patients) or medical treatment (158 patients). Patients were followed up prospectively for up to 15 years. Seven patients were lost during follow-up. The primary outcome was a composite of stroke, transient ischemic attack, or peripheral embolism. We analyzed 103 propensity score-matched pairs of patients who underwent percutaneous PFO closure or medical treatment. At a median follow-up of 9 years, the primary composite outcome occurred in 11 patients slated to PFO closure (11%) and 22 patients slated to medical treatment (21%; hazard ratio=0.43; 95% confidence interval=0.20-0.94; P=0.033). The treatment effect was driven by a decrease in the risk of transient ischemic attack of 5% versus 14%, respectively (hazard ratio=0.31; 95% confidence interval=0.10-0.94; P=0.039). The risk of all-cause (6% in both groups) and cardiovascular (3% in both groups) mortality appeared to be identical. Conclusion--In this long-term observational, propensity score-matched study, percutaneous PFO closure was more effective than medical treatment for the secondary prevention of recurrent cerebrovascular events among patients with PFO-related transient ischemic attack or stroke. [ABSTRACT FROM AUTHOR]