PROJECT SUMMARY Tracheal Intubation (TI) is a common life-saving intervention for resuscitation of critically ill infants in Neonatal Intensive Care Units (NICUs). Through our NICHD-funded NICU multicenter registry (National Emergency Airway Registry for Neonates: NEAR4NEOS), we have identified that Adverse TI Associated Events (TIAEs) occur in 22% TIs, severe TIAES occur in 4% TIs, and multiple attempts occur in 23% TIs. Oxygen desaturations (captured separately from TIAEs) are frequent and pronounced, with a mean 28% decline in SpO2 during neonatal TI. Moreover, neonates who experienced adverse TIAEs were at higher risk of extubation failure and NICU mortality. We have identified key factors strongly associated with adverse TIAEs: 1) patient risk, 2) provider skill, 3) premedication with paralysis, and 4) video laryngoscopy. We have developed, refined, and tested a Personalized Intubation Safety (PINS) Bundle aimed at addressing these factors and prompting a prospective plan for TI management. The prototype Safety Bundle resulted in a sustained 66% reduction in severe TI adverse events in our pilot single center study. In this proposal, we will perform a pragmatic stepped wedge cluster randomized trial across 8 NEAR4NEOS NICUs to assess the impact of the Personalized Intubation Bundle on TI safety events. The timing of introducing the Bundle intervention will be randomized at the NICU site level. Our primary outcome is adverse TIAEs; secondary outcomes are severe TIAEs, multiple (>2) attempts, and magnitude of oxygen desaturation. We will test whether there is a significant variability in the treatment effect of the PINS Bundle based on the airway provider skill. This will provide important information about the impact of the Bundle intervention and its components for novice vs. experienced providers, which will help NICUs to contextualize study findings. Finally, we will explore the impact of the PINS Bundle intervention on relevant NICU patient outcomes, including extubation failure, duration of mechanical ventilation, intraventricular hemorrhage, and NICU mortality. Upon successful completion of this project, we will establish the effectiveness of a prospective Personalized Intubation Safety Bundle to reduce adverse events, multiple attempts and oxygen desaturation during neonatal TI. These results will generate a paradigm shift to improve neonatal intubation procedural safety.