Previous studies have suggested that the closure of the patent foramen ovale (PFO) may reduce or resolve migrainous symptoms, but ideal indications, devices and techniques are far from being identified definitively. A 21-year-old woman was referred to our center for evaluation of severe migraine (more than two attacks per week, > 6 h in duration, inability to work, direct relationship with Valsalva manouvre and effort, presence of aura), migraine disability assessment questionnaire (MIDAS) score of 42 and a large PFO with no atrial septal aneurysm: on transesophageal echocardiography and instrumental data suggesting a close relationship between migraine and PFO. Having explained the off-label indications for transcatheter PFO closure in this particular case, the patient was recruited for our in-hospital study protocol for assessment for transcatheter closure of PFO to relieve severe migraine and the patient gave consent. A 9-Fr, 9-MHz UltraICE catheter (EP Technologies, Boston Scientific Corporation, San Jose, California, USA) was then inserted through the left femoral vein and a complete intracardiac study was carried out. A 25-mm Premere device was successfully implanted. The patient was discharged the day after being on 75 mg aspirin once a day for 6 months and, at 3-month follow-up, the patient was well with no further migraine attacks (MIDAS score 2). There was no evidence of thrombus formation on the surface of device and no shunt was detected on transesophageal echocardiograhy and transcranial Doppler. Although more clear-cut indications are required, this case study may be the stimulus and basis for further large prospective randomized studies to assess the effectiveness of PFO closure in treating migraine and the best implantation technique and device.