ABSTRACT The overarching goal of this R21 Grant proposal is to identify the optimal timing of prehospital advance life support (ALS) interventions for patients with out-of-hospital cardiac arrest (OHCA). The ALS interventions include advanced airway management (AAM: i.e., endotracheal intubation and supraglottic airway placement) and epinephrine administration. OHCA is a major public health problem worldwide, annually affecting over 356,000 Americans with substantially high rates of mortality and functional disability. Emergency medical services (EMS) play an important role for patients with OHCA by providing initial prehospital care, including the ALS interventions in the field. However, the optimal timing of the ALS interventions remains unclear. The 2019 International Liaison Committee on Resuscitation (ILCOR) Summary Statement, International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations identified the optimal time of both AAM and epinephrine administration as key knowledge gaps. We recently found that, for adults with both shockable and nonshockable rhythms, benefit of epinephrine decreased as the administration was delayed, using the Resuscitation Outcomes Consortium (ROC) registry, a large multicenter OHCA registry in the United States and Canada. This R21 Grant project proposes to further expand our research into AAM and pediatric population, analyzing the ROC data. Specific research Aims include identifying the optimal timing of AAM (Aim 1A) and endotracheal intubation (Aim 1B) for adult patients with OHCA, the optimal timing of AAM (Aim 2A) and endotracheal intubation (Aim 2B) for pediatric patients with OHCA, and the optimal timing of epinephrine (Aim3) for pediatric patients with OHCA. This R21 Grant application will provide the Principal Investigator (PI) with protected time to achieve research aims to improve outcomes for patients with OHCA. The results of this R21 proposal will provide crucial information on the timing of ALS interventions for OHCA and inform future national and international resuscitation guidelines.