COR LOE Recommendations In patients with a nonlacunar ischemic stroke of undetermined cause and a PFO, recom- mendations for PFO closure versus medical management should be made jointly by the patient, a cardiologist, and a neurologist, taking into account the probability of a causal role for the PFO. In patients 18 to 60 years of age with a nonla- cunar ischemic stroke of undetermined cause despite a thorough evaluation and a PFO with high-risk anatomic features,* it is reasonable to choose closure with a transcatheter device and long-term antiplatelet therapy over anti- platelet therapy alone for preventing recurrent In patients 18 to 60 years of age with a nonla- cunar ischemic stroke of undetermined cause despite a thorough evaluation and a PFO without high-risk anatomic features,* the ben- efit of closure with a transcatheter device and long-term antiplatelet therapy over antiplatelet therapy alone for preventing recurrent stroke is not well established,552 557 In patients 18 to 60 years of age with a nonlacunar ischemic stroke of undetermined cause despite a thorough evaluation and a PFO, the comparative benefit of closure with a transcatheter device versus warfarin is *In the evidence, each study defines high-risk anatomic features in a different way. Synopsis Substantial epidemiological evidence suggesting a causal role of PFO for stroke led to randomized trials of PFO device closure in patients <60 years of age with stroke of undetermined origin. The first 3 trials558 560 compared device closure with either antiplatelet or anti- coagulant treatment, and 2 of these558,560 showed a non- significant trend toward benefit of device closure. Two compared device closure with antiplatelet treatment alone, and each trial showed a significant benefit of PFO closure. 