Patent foramen ovale (PFO) has been reported to be associated with cryptogenic stroke in young patients. Earlier trials evaluating PFO closure as a secondary prevention strategy for stroke did not show any significant benefit. In September, 2017, three large randomized trials were published showing superiority of PFO closure over standard medical therapy in prevention of recurrent stroke. In this manuscript, we review the possible reasons underlying the difference in outcomes between the earlier and recent trials. While PFO closure should not be routinely performed in all patients with cryptogenic stroke and a PFO, it is reasonable to consider this for younger patients witha high risk of paradoxic embolism, especially with a large PFO and at least moderate right- to- left shunt.