Background: Perioperative anaphylaxis (PA) in children is an uncommon but potentially life-threatening complication associated with anesthesia. Early identification and management of PA is essential to optimize clinical outcomes. Methods: We performed a retrospective study of anesthesia records from pediatric patients with PA from centers in the United Kingdom, France, and the United States over a period of 10 years. Time sequence of clinical signs and physiological variables during PA were collected, along with results of allergy testing. Results: Twenty-nine children with PA were included. Median age was 11 years. Based on the modified Ring and Messmer Grading Scale, severe reactions were seen in 25 (86%) members of this cohort, with 4 (14%) experiencing cardiac arrest. Life-threatening hypotension was the first clinical sign of PA in 59% of cases, followed by tachycardia and bronchospasm. In 16 (55%) cases, the initial signs of PA involved multiple organ systems. When the initial signs of PA were cardiovascular and/or respiratory, more epinephrine doses were administered. Average time from initial sign of PA to treatment with epinephrine was 6 minutes (SD: 6, range: 1-25). The causative allergen was identified in 15 patients. Conclusion: Severe hypotension is the most common presenting sign of PA in children. Initial cardiovascular and/or respiratory signs are associated with the need for increased epinephrine doses. Further studies should optimize the prediction, identification, and early management of PA in children.