INTRODUCTION: Deaths of opioid overdose are a serious public health concern throughout the U.S., transcending geographical and demographic categories. While naloxone can reverse an overdose and prevent death, it must be administered in a timely fashion. Efforts to get naloxone widely distributed contribute to harm reduction efforts, but more efficient strategies for recruiting people to carry and administer naloxone will increase the impact and advance prevention science. Yet, most existing programs are not evidence-based. The Opioid Rapid Response System (ORRS) was developed for these purposes. METHODS: A randomized controlled trial will be conducted in 9 communities in Pennsylvania, Arizona, and Washington to evaluate ORRS. The RCT will be conducted with pretest and posttest surveys administered to assess the effectiveness of the training. Focus groups will inform the development of the ORRS training. To increase the appeal of naloxone training for volunteers, recruitment strategies will focus on personal and social identity. CONCLUSION: The Opioid Rapid Response System is a theory-driven program that recruits and trains lay citizens to respond to opioid overdose events. The program has the potential to advance knowledge of lay citizen recruitment and training, and to reduce deaths from overdoses. TRIAL REGISTRATION: NCT06238128.