Abstract: Patent foramen ovale (PFO) is a common development anomaly that allows for the passage of blood and other substances from the right-sided (venous) to the left (arterial) circulation. During recent years, the pathogenic effects of PFO have aroused the attention of experts and scholars. PFO is associated with cryptogenic stroke, migraine and platypnea orthodeoxia syndrome, but uncertainty remains about the exact relationship and the best management. Percutaneous closure of PFO is safe and effective, and this procedure has been definitely proven to be better than medical therapy. Paradoxical embolism is a rare event occurring over decades rather than years. None of the 4 randomized trials published carried enough patients or was followed up for long enough to reach superiority endpoints. All data, however, point to a benefit of PFO closure. They are outweighed by the supposedly prevented events of paradoxical embolisms, such as stroke, transient ischemic attacks, or other systemic embolisms. Medical treatment with perhaps the exception of lifelong oral anticoagulation provides less protection. A 10-year follow-up of a comparative study reports that the annual mortality in the patients with PFO closure (0.4%) is significantly lower than that in those with medical treatment (1.1%, P<0.05). However, the evidence-based research is still controversia.