Background <p>Migraine is a complex neurological disorder marked by severe headache and associated with various systemic symptoms. Atrial septal defect (ASD) closure, a common cardiac procedure, has been linked to the onset of new migraine episodes. This systematic review explores the incidence and management of migraine following transcatheter ASD closure.</p> Methods <p>A comprehensive literature search was conducted in PubMed, Scopus, and CINAHL Ultimate, covering studies from inception to August 2024. The review followed PRISMA guidelines and was registered on PROSPERO (CRD42024578609). Data extraction and risk of bias assessment were systematically performed by independent reviewers.</p> Results <p>A total of 831 studies were identified out of which 13 were included for the final analysis. The studies encompassed diverse populations globally, revealing varying onset times for migraine post-ASD closure, ranging from as early as 1&#xa0;day to up to a year. Migraine incidence varied significantly, with several studies noting a higher prevalence in females and some cases showing a familial predisposition typically in the maternal side. The typical methods for ASD closure involved transcatheter approaches. Treatment modalities included non-steroidal anti-inflammatory drugs, calcium channel blockers, and anticoagulants, with some cases experiencing spontaneous resolution of symptoms. Modifications to anti-platelet therapy post-procedure, such as the introduction of clopidogrel along with aspirin, showed significant efficacy in treating and preventing migraine.</p> Conclusion <p>This review highlights a significant correlation between ASD closure and the onset of migraine, underlining the need for further investigation into preventive strategies and management. These findings suggest a complex interaction between structural heart alterations and migraine pathophysiology.</p>