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Background: The "interictal burden of migraine" (MIB) is a new concept that encompasses the overall impact of the disease between migraine episodes. However, the factors that contribute to this interictal burden are still unclear., Objective: This study aimed to identify explanatory factors of interictal burden in patients with migraine., Methods: This prospective cross-sectional observational including 200 patients with migraine (92% [n = 184] female, with a mean [standard deviation] age of 44.8 [12] years, 53% [n = 106] with chronic migraine) completed a clinical and questionnaire assessment targeting MIB, migraine impact, and depressive and cognitive complaints., Results: More than three-fourths (76% [n = 152]) of patients had moderate-to-severe interictal burden. Higher interictal burden (MIB Scale ≥2) was associated with higher headache frequency (eight vs. 14, p = 0.001) and intensity (headache index score 17.0 vs. 30.0, p = 0.002), higher headache impact (six-item Headache Impact Test score 59.2 vs. 63.9, p = 0.001), and more subjective memory complaints (Subjective Memory Complaints Questionnaire [SMC] score 9.0 vs. 4.5, p = 0.001), as well as anxiety (Hospital Anxiety and Depression Scale (HADS)-Anxiety score 5 vs. 10, p < 0.001) and depression symptoms (HADS-Depression score 5 vs. 8, p < 0.001). Once accounted for these potential explanatory variables, subjective memory complaints and impact of headache during ictal phase remained as individual determinants of the interictal burden, with SMC explaining 15% (odds ratio 1.15, 95% confidence interval 1.03-1.28; p = 0.010) of the interictal burden., Conclusion: This finding highlights the need to consider cognitive complaints as part of the construct of interictal burden of these patients to refine the focus of their management., (© 2024 American Headache Society.)