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Background: Food-related anaphylactic reactions may require treatment with more than 1 dose of epinephrine. Current guidelines advise patients at risk of anaphylaxis to carry 2 epinephrine autoinjectors., Objective: The objective of this study was to determine risk factors of multiple-dose epinephrine treatment in pediatric food-related anaphylaxis., Methods: Parents of children with physician-confirmed diagnosis of food allergy were administered a standardized questionnaire at the time of their clinic visit. These patients were then followed-up prospectively by phone., Results: Six hundred forty-two subjects had allergic reactions. Twenty-six percent of patients reported at least 1 reaction treated with epinephrine, for a total of 221 reactions. Among reactions treated with epinephrine, 24 reactions (11%) received 2 or more doses of epinephrine. The most common triggers were milk (30%) and peanut (18%). Milk-triggered allergic reactions (odds ratio [OR] 3.2; 95% confidence interval [CI] 1.2-8.4) and treatment with oxygen (OR 5.0, 95% CI 2.0-12.4) were significant risk factors for requiring multiple doses of epinephrine to treat an allergic reaction., Conclusion: This study demonstrates that treatment of anaphylaxis may require more than 1 epinephrine injection. Reactions triggered by milk or requiring treatment with oxygen are at higher risk for needing more than 1 dose of epinephrine. Families of food-allergic children should be counseled on the importance of carrying 2 epinephrine auto-injectors., (Copyright © 2018  . Published by Elsevier Inc. All rights reserved.)