Background: De novo onset or aggravation of migraine has been observed after atrial septal defect closure (ASDC), whereas antiplatelet drugs, such as clopidogrel, used to prevent post-ASDC thromboembolic events, have been associated with migraine amelioration. Case: We report the case of a woman who, after ASDC, experienced de novo severe migraine with aura. Whereas use of acetylsalicylic acid or clopidogrel had no effect, ticlopidine use was associated with migraine amelioration. Migraine relapsed after two ticlopidine dechallenges, and disappeared after drug rechallenges. Conclusion: A ticlopidine trial could be proposed to patients with migraine which occurs or worsens immediately after ASDC and does not improve with clopidogrel.