In response to the national opioid public health crisis, NIH has launched the HEAL (Helping to End Addiction Long-term) Initiative, which intends to speed research that will improve treatment for addiction and enhance pain management. The HEAL Pain Management Effectiveness Research Network (ERN) is a key component of the initiative and to be successful, these ERN trials will need to efficiently recruit participants and minimize dropouts. To ensure HEAL Pain ERN studies accrue and retain the number and diversity of participants required to assess primary and secondary outcomes, we propose a Supplement to the Recruitment Innovation Center to support the development of a robust recruitment infrastructure, complete with the tools, resources, and innovative strategies needed to proactively address recruitment barriers and rapidly identify and mitigate emerging roadblocks across sites. Led by Paul Harris, PhD and Consuelo H. Wilkins, MD, MSCI, this supplement will focus on supporting and incorporating recruitment and engagement expertise through all study stages (design, planning, protocol development, start-up, implementation, and dissemination) to accurately assess recruitment feasibility, minimize challenges, and optimize recruitment, retention, and return of value to all participants. We will leverage existing resources available in the Recruitment Innovation Center (RIC) and capitalize on important thematic areas of competency of our team that includes; 1) participant-centered approaches that recognize varying needs and preferences of individuals with pain; 2) multifaceted approaches that combine informatics tools and contextual data sources and systems (e.g. electronic health records) to guide comprehensive recruitment strategies; 3) engagement of patients, community groups and clinicians in all stages of the studies; and 4) application of existing and novel recruitment methods and tools to advance the evidence base for best practices in recruiting these populations. The overarching goal of this supplement is to aid in the efficient recruitment and retention of a diverse sample of participants for HEAL Pain clinical trials. We will leverage the vast expertise and centralized infrastructure of the RIC and collaborate with each of the three Trial Innovation Centers (TICs) to support NIH’s trans-agency efforts to develop scientific solutions to the national opioid crisis.