Given increasing opioid overdose mortality rates in the USA over the past 20 years, accelerating the implementation of prevention interventions found to be effective is critical. The Helping End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is a consortium of research projects funded to implement and test interventions designed to prevent the onset or escalation of opioid misuse among youth and young adults. The HPC offers a unique opportunity to synthesize and share lessons learned from participating research projects' varied implementation experiences, which can facilitate quicker integration of effective prevention interventions into practice. This protocol paper describes our hybrid approach to collecting and analyzing information about the implementation experiences of nine of the HPC research projects while they maintain their focus on assessing the effectiveness and cost-effectiveness of prevention interventions. To better understand implementation within this context, we will address five research questions: (1) What were the context and approach for implementing the prevention interventions, and how was the overall implementation experience? (2) How representative of the target population are the participants who were enrolled and retained in the research projects' effectiveness trials? (3) For what purposes and how were stakeholders engaged by the research projects? (4) What are the adaptable components of the prevention interventions? And finally, (5) how might implementation of the prevention interventions vary for non-trial implementation? This work will result in intervention-specific and general practical dissemination resources that can help potential adopters and deliverers of opioid misuse prevention make adoption decisions and prepare for successful implementation.