To examine risk factors of multiple-dose epinephrine treatment in pediatric food-induced anaphylaxis.In a total of 642 surveys, participants reported allergic reactions. The median age of the child was 2.5 years, 59% were boys, and 77% were white. Allergy to peanut and tree nut were the most common in this population. Prospective follow-up data were collected from the same respondents at median age 7.5 years.Between 2009 and 2011, families of children with food allergy at the Jaffe Food Allergy Institute were randomly selected to complete a questionnaire evaluating demographics, atopic history, and number of reactions requiring epinephrine. Follow-up data on reaction details were prospectively collected.History of asthma or report of respiratory symptoms during a reaction increased the odds of requiring any epinephrine. Eleven percent of reactions required multiple doses of epinephrine. Milk-triggered reactions were 3 times more likely to require multiple doses of epinephrine than reactions caused by other foods. In reactions that required multiple doses of epinephrine, the initial dose was more likely to be given by emergency medical services, not a child’s immediate caregiver. Reactions managed with oxygen were also more likely to require more than 1 dose of epinephrine.This is the first study evaluating the need for multiple doses of epinephrine in young pediatric patients. A significant number of food-induced anaphylaxis cases required multiple doses of epinephrine, especially those triggered by milk or treated with oxygen, and 11% of the children required multiple doses of epinephrine. This emphasizes the importance of carrying 2 autoinjectors.Although nut allergy was the most common reported allergy, reactions to milk were the most likely to require multiple doses of epinephrine in this young cohort. Families often separate the autoinjectors in a kit and must be counseled on the importance of having 2 autoinjectors available at all times. Caregivers must be empowered to administer epinephrine immediately in cases of anaphylaxis. Prompt epinephrine administration, occasionally multiple doses, is paramount and lifesaving.