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Background: Patent foramen ovale closure in the setting of stroke was debatable until the recent data from the long-term follow-up of multiple randomized control trials. These recent data have led to increase the number of the procedure worldwide. To our knowledge, there was no previous formal structured program in Egypt between cardiologists and neurologists for investigation and management of patients with cryptogenic stroke. The first Egyptian-dedicated stroke team was created in two large tertiary centers with collaboration between cardiologists, dedicated cardiac imagers, and neurologists for investigation and management of patients with cryptogenic stroke. Results: Sixty-three patients with cryptogenic stroke were identified from a total of 520 patients admitted to the stroke units between 2016 and 2019. Twenty-five patients had a proven PFO-related stroke. Three patients were referred for surgical closure, 19 patients underwent transcatheter PFO closure, and procedural success was met in 18 patients (94.7%). We did not experience any major procedure-related complication. Complete closure was achieved in 83.3% of patients at 6 months. One patient had a single attack TIA within the first 3 months after device closure; one patient had a device-related thrombosis; both were managed successfully. Conclusion: Our initial experience in collaboration between cardiologist and neurologist with the establishment of a dedicated cryptogenic stroke team added significantly to the management of patients with stroke. The results of the first Egyptian cohort who underwent transcatheter PFO closure demonstrated procedural feasibility, safety, and efficacy with very low incidence of major complications. A nationwide program is needed to reduce the ischemic stroke disease burden and the risk of recurrence. [ABSTRACT FROM AUTHOR]