Objective: The objective of this study was to quantify and characterize patient safety events during high-risk neonatal transports in the prehospital setting. Method: We conducted a retrospective chart review of all "lights and sirens" ambulance transports of neonates ࣘ30 days old over a four-year period in a metropolitan area. Each case was independently reviewed for potential patient safety events that may have occurred in clinical assessment and decision making, resuscitation, airway management, fluid or medication administration, procedures performed, and/or equipment used. Results: Twenty-six patients ࣘ30 days old were transported by ambulance using lights and sirens during the four-year study period. Overall, safety events occurred in 19 patients and severe safety events (potentially causing permanent injury or harm, including death) occurred in ten. The incidence of safety events related to medication administrations was 90% (70% severe), resuscitation 64.7% (47.1% severe), procedures 64.7% (35.3% severe), fluid administration 50% (25% severe), clinical assessment and decision making 50% (30.8% severe), airway management 47.6% (28.6% severe), equipment use 25.5% (10.0% severe), and systems processes 19.2% (7.7% severe). Conclusions: High-risk neonatal calls are infrequent and prone to a high incidence of serious patient safety events.