Background: Patent foramen ovale(PFO) has been implicated in the etiology of migraine headache with aura(MHA), but the mechanisms that link right-to-left(R-to-L) shunt to MHA are unclear, and the reports on the efficacy of transcatheter PFO closure on MHA prevention are scarce. Methods: We reviewed the clinical records of 131 consecutive patients who underwent successful transcatheter PFO closure at our institution at a mean age of 45±13 years because of cryptogenic stroke. Of the 131 patients, 35(27%) had a diagnosis of MHA made by the primary care physician or the referring neurologist. Migraine headache with aura incidence and severity were assessed by using Migraine Disability Assessment(MIDAS) questionnaire. Presence and magnitude of R-to-L shunt were assessed in all patients by means of transesophageal echocardiography and also by means of transcranial Doppler(TCD) in the last 50 patients(38%). Results: Patients with MHA had a higher prevalence of thrombophilia(P=.007), a more complex atrial septal anatomy(P=.001), and they also had higher prevalence of spontaneous R-to-L shunt and of spontaneous large shunt,both at transesophageal echocardiography(P=.015, and .028, respectively) and at TCD(P=.036, and .038, respectively). After the procedure, 32(91%) of 35 patients had either complete resolution or significant improvement in their MHA. At a mean follow-up of 1.7±1.3 years, MHA disappeared completely in 29(83%) of 35 patients. Of the remaining 6 patients, 3 patients(8%) had an improvement of ≥2 grades in the incidence and severity of MHA, 2 patients did not show any improvement of their MHA, whereas 1 patient reported a severe relapse of MHA about 1 year after the procedure. Conclusions: In patients with PFO, MHA is associated with spontaneous large R-to-L shunt and thrombophilic conditions. Transcatheter defect closure seems to be an effective and safe means to treat MHA in patients with PFO. Background: Patent foramen ovale (PFO) has been implicated in the etiology of migraine headache with aura (MHA), but the mechanisms that link right-to-left (R-to-L) shunt to MHA are unclear, and the reports on the efficacy of transcatheter PFO closure on MHA prevention are scarce. Methods: We reviewed the clinical records of 131 consecutive patients who underwent successful transcatheter PFO closure at our institution at a mean age of 45 ± 13 years because of cryptogenic stroke. Of the 131 patients , 35 (27%) had a diagnosis of MHA made by the primary care physician or the referring neurologist. Migraine headache with aura incidence and severity were assessed by using Migraine Disability Assessment (MIDAS) questionnaire. Presence and magnitude of R-to-L shunt were assessed in all patients by means of transesophageal echocardiography and also by means of transcranial Doppler (TCD) in the last 50 patients (38%). Results: Patients with MHA had a higher prevalence of thrombophilia (P = .007), a more c omplex atrial septal anatomy (P = .001), and they also had higher prevalence of spontaneous R shunt and of spontaneous large shunt, both at transesophageal echocardiography (P = .015 and .028, respectively) and at TCD After the procedure, 32 (91%) of 35 patients had either either complete resolution or significant improvement in their MHA. At a mean follow-up of 1.7 ± 1.3 years, MHA disappeared Of the remaining 6 patients, 3 patients (8%) had an improvement of ≧ 2 grades in the incidence and severity of MHA, 2 patients did not show any improvement of their MHA, but completely in 29 (83%) of 35 patients. 1 patient reported a severe relapse of MHA about 1 year after the procedure. Conclusions: In patients with PFO, MHA is associated with spontaneous large R-to-L shunt and thrombophilic conditions. Transcatheter defect closure seems to be an effective and safe means to treat MHA in patients with PFO.