<h3>Objective:</h3> The objective of this study is to explore the relationship between anxiety and depressive symptoms and migraine outcomes over time in children and adolescents. <h3>Background:</h3> Youth with migraine have more anxiety and depressive symptoms than their peers, but it is unknown if these impact migraine outcomes. <h3>Design/Methods:</h3> In this prospective longitudinal clinical cohort study, children and adolescents with migraine completed headache questionnaires and validated measures of anxiety and depressive symptoms (PROMIS) at an initial consultation and at their first follow-up visit with a neurologist. Migraine outcomes were the change in monthly headache frequency, and the change in migraine-related disability (PedMIDAS). The relationships between longitudinal migraine outcomes and baseline anxiety and depressive symptoms were estimated using multiple linear regression models controlling for sex, age, headache frequency, and treatment type. A priori sample size calculations were completed and we estimated that a sample size of n=118 was required to determine if baseline mental health symptoms would be associated with migraine outcomes (effect size=0.35, β=80%, α=0.05, 6 covariates). <h3>Results:</h3> Data were collected from 120 consenting participants. Baseline anxiety and depressive symptom levels were not significantly associated with change in headache frequency, nor with change in disability in univariate nor in multiple linear regression models (p>0.05). In post-hoc exploratory analyses (N=72 that had complete anxiety and depressive symptom data at both visits), there was a significant association between change in migraine-related disability and change in anxiety symptoms between visits in multivariable models (ß=1.10, 95% CI=0.045–2.16, p=0.04). <h3>Conclusions:</h3> We found no relationship between baseline anxiety and depressive symptom levels and longitudinal migraine outcomes; this contradicts popular clinical belief that mental health symptoms predict migraine outcomes in children and adolescents. However, as disability improved, so did anxiety symptoms; this finding requires replication. <b>Disclosure:</b> Mr. Rizvi has received research support from University of Calgary . The institution of Ms. Cho has received research support from Canadian Institutes of Health Research. Mr. Kuziek has nothing to disclose. Dr. Ronksley has nothing to disclose. Dr. Noel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Society of Pediatric Psychology. Dr. Noel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for PAIN. Dr. Noel has received research support from CPCoE. The institution of Dr. Orr has received research support from Alberta Children’s Hospital Research Institute. The institution of Dr. Orr has received research support from Canadian Institutes of Health Research. Dr. Orr has received publishing royalties from a publication relating to health care. Dr. Orr has a non-compensated relationship as a Associate Editor with Headache: The Journal of Head and Face Pain that is relevant to AAN interests or activities. Dr. Orr has a non-compensated relationship as a Editorial Board with Neurology that is relevant to AAN interests or activities.