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Recent randomized control trials (RCTs) have suggested benefit with transcatheter patent foramen ovale (PFO) closure plus antiplatelet therapy over medical treatment alone for secondary stroke prevention.Data sources: we searched PubMed and Ovid MEDLINE from the inception until November 10, 2017 for RCTs comparing TPFO closure to medical therapy in patients with a PFO and a history of cryptogenic stroke.Five RCTs with 3,627 patients (TPFO closure = 1,829 versus medical therapy =1,798) were included. There was a decreased number of post-TPFO closure strokes compared to the medical therapy arm; 53 versus 80 strokes (odds ratio [OR] = 0.61, CI: 0.39-0.94, P = 0.03, I2 = 17%). Transient ischemic attacks occurred in 43 patients after TPFO closure versus 60 patients in the medical therapy group (OR = 0.80, CI: 0.53-1.19, P = 0.26, I2 = 0%). There was a higher incidence of atrial fibrillation in the TPFO closure group, which occurred in 75 patients, compared to 12 patients in the medical therapy group (OR = 5.23, CI: 2.17-12.59, P = 0.0002, I2 = 43%). There was a trend toward a decreased number of neuropsychiatric events in the TPFO closure closure group compared to the medical therapy group; 42 versus 67 neuropsychiatric events (OR = 0.71, CI: 0.48-1.06, P = 0.09, I2 = 0%).TPFO closure plus antiplatelet therapy is superior to medical therapy in patients with a PFO and cryptogenic stroke. PFO closure is associated with new-onset atrial fibrillation and a trend toward reduced neuropsychiatric events.