Background Objective Methods Results Conclusion 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.This study aimed to identify explanatory factors of interictal burden in patients with migraine.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.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.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. [ABSTRACT FROM AUTHOR]