This study aims to evaluate the potential of percutaneous patent foramen ovale (PFO) closure to improve the headache in patients with migraine and PFO, and discuss the difference between the randomized controlled trials (RCTs) and the single-center studies. Patients of migraine with a large shunt of PFO, who experienced ≥2 headache attacks per month and failed ≥2 categories of standardized medication, underwent PFO closure in First Affiliated Hospital of Xi’an Jiao Tong University. The clinical outcomes, including frequency and duration of headache attacks, Headache Impact Test (HIT-6) score, and Visual Analogue Scale (VAS) score, were evaluated at 3, 6, and 12 months of follow-up after the PFO closure. The different efficacies of the clinical outcomes between patients with and without aura as well as different grades of PFO were also evaluated, respectively. 134 patients with migraine (39 male and 95 female) with PFO were enrolled, whose average age was 39.21±11.37 years. After PFO closure, there was a significant reduction in frequency and duration of headache attacks, HIT-6 score, and VAS score at 3, 6, and 12 months’ follow-up (p50% in 44 (32.84%) patients at 3 months’ follow-up and increased to 48 (35.82%) at 12 months’ follow-up. 31.03% patients remained residual shunt after 6 months of closure with varying improvements of headache. This study confirmed that PFO closure can effectively reduce frequency and duration of migraine and improve quality of life, but the definitive indications and long-term effect still need further research.© American Federation for Medical Research 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.