PROJECT SUMMARY/ABSTRACT Migraine affects over 47 million Americans and is the second most disabling condition globally. Healthcare utilization rates for migraine are high, with over six million ambulatory visits annually in the US. More than half of these visits occur in primary care settings. One in ten primary care consultations is for headache, and migraine accounts for at least 75% of these headache visits. Despite evidence that mind-body interventions (MBIs) are effective for migraine, these treatments are vastly under-utilized due to limited provider availability as well as patient-reported barriers, such as time and expense. Access to MBIs is quite limited in primary care settings where most people receive treatment. New scalable, accessible, and evidence-based MBIs are needed. Our team conducted multiple pilot studies in many settings to evaluate delivery of progressive muscle relaxation (PMR) for migraine in a patient-centered smartphone application (app) “RELAXaHEAD”. Our successful recruitment (over 300 patients to migraine RELAXaHEAD pilot studies and over 200 patients to other migraine mind-body studies), proven track record of conducting mobile health (mHealth) studies (8 publications using RELAXaHEAD), and expertise in headache medicine, MBIs, clinical trial design, and adherence collectively position us optimally to expand on this work. In response to the NIH prioritization of research on chronic overlapping pain conditions and the recent call for fully remote MBI studies, we seek to conduct a fully powered, entirely remote study to assess the efficacy of RELAXaHEAD (RELAX, app with diary and PMR) compared to monitored usual care (MUC, app with diary) over a 6-week period (based on prior PMR studies which showed benefit of PMR at 6 weeks). We will compare clinically meaningful patient-reported outcomes in patients randomized to RELAX vs. MUC. Outcomes include change in migraine-related disability, migraine-specific quality of life, and headache days. We will assess both the short-term effects (after 6 weeks of treatment) and the persistence of benefits for up to 26 weeks following enrollment. We will also explore both potential mediators of treatment effect (improvement in depression, anxiety, sleep) and potential moderators (age, sex, race, ethnicity, and education level). We will recruit from primary care faculty group practices and family health centers in a large academic healthcare system to include a very wide range of patients with migraine, spanning diverse racial backgrounds and ethnicities, and from both urban and suburban communities. The long-term goal of the research is to create an evidence-based, scalable, and accessible MBI for migraine with far-reaching impact in a low-cost manner to improve migraine-related disability, improve quality of life in people with migraine, and reduce headache days.