From the abstract: "The Helping to End Addiction Long-term (HEAL) Prevention Collaborative (HPC) is designed to expedite the development of programs aimed at preventing opioid misuse and opioid use disorder (OUD) in older adolescents and young adults (ages 16–30). Funded by the National Institutes of Health Office of the Director (ODP-NIH), the HPC includes ten outcome studies that focus on distinct interventions to determine their effectiveness and real-world applicability. Also included is a coordinating center at RTI International that supports the individual projects. This commentary highlights the scientific and practical significance of this cooperative and its promise for facilitating the production and implementation of successful interventions. Attributes such as novel program designs, advanced methodologies, addressing unique characteristics of diverse populations, and real-time analysis of data and costs make this cooperative highly innovative. We note, however, that papers in this Supplemental Issue did not specifically address the persistent need to obtain stronger effect sizes than those achieved to date. Existing data captured earlier in development (