Transcatheter patent foramen ovale (PFO) closure might be effective in improving migraines. To assess the efficacy of PFO closure in migraineurs with a moderate to large right-to-left shunt and instrumental evidence of embolic cerebral damage, 76 highly symptomatic migraineurs were prospectively investigated. The presenting clinical syndrome was stroke in 16 patients, repeated transient ischemic attack in 32 patients, and lone migraine associated with cerebral ischemic lesions on magnetic resonance imaging in 28 patients. Migraine severity was assessed before PFO closure and monthly for 6 months after discontinuation of antiplatelet therapy. At the end of 12 months of follow-up, the averaged postprocedural total score was compared with the baseline score. Transcatheter PFO closure was successful in all patients, and the 12-month PFO closure rate was 97%. The baseline total migraine score was similar in patients with stroke, transient ischemic attack, and lone migraine (6.8 +/- 1.6, 6.7 +/- 1.4, and 6.9 +/- 1.7 respectively, p = NS). After a mean follow-up of 13.7 +/- 2.4 months, no recurrent cerebrovascular episodes had occurred. At the end of the follow-up period, a significant reduction in the total migraine score was observed in all groups, regardless of the initial clinical presentation. Migraine was completely abolished in 35 patients (46%), improved in 27 (36%), and unchanged in 14 (18%). The proportion of patients with migraine suppression and improvement was similar in the 3 groups. In conclusion, in highly symptomatic migraineurs with previous ischemic cerebral events and instrumental evidence of cerebral embolism, transcatheter PFO closure can result in improvement of migraine severity in a high percentage of patients.