OBJECTIVES: In this study, a meta-analysis of observational studies was performed to compare the rate of recurrent neurological events (RNE) between transcatheter closure and medical management of patients with cryptogenic stroke/transient ischemic attack (TIA) and concomitant patent foramen ovale (PFO). BACKGROUND: A significant controversy surrounds the optimal strategy for treatment of cryptogenic stroke/TIA and coexistent PFO. METHODS: We conducted a MEDLINE search with standard search terms to determine eligible studies. RESULTS: Adjusted incidence rates of RNE were 0.8 (95% confidence interval [CI]: 0.5 to 1.1) events and 5.0 (95% CI: 3.6 to 6.9) events/100 person-years (PY) in the transcatheter closure and medical management arms, respectively. Meta-analysis of the limited number of comparative studies and meta-regression analysis suggested that the transcatheter closure might be superior to the medical therapy in prevention of RNE after cryptogenic stroke. Comparison of the anticoagulation and antiplatelet therapy subgroups of the medical arm yielded a significantly lower risk of RNE within patients treated with anticoagulants. Device-related complications were encountered at the rate of 4.1 (95% CI: 3.2 to 5.0) events/100 PY, with atrial arrhythmias being the most frequent complication. After transcatheter closure, RNE did not seem to be related to the pre-treatment shunt size or the presence of residual shunting in the follow-up period. Significant benefit of transcatheter PFO closure was apparent in elderly patients, patients with concomitant atrial septal aneurysm, and patients with thrombophilia. CONCLUSIONS: Rates of RNE with transcatheter closure and medical therapy in patients presenting with cryptogenic stroke or TIA were estimated at 0.8 and 5.0 events/100 PY. Further randomized controlled trials are needed to conclusively compare these 2 management strategies.