BACKGROUND Given the increase in childhood food allergy, national and local policies have been developed to encourage schools to stock undesignated epinephrine auto-injectors in case of an anaphylactic emergency. PURPOSE To describe the use of epinephrine auto-injectors in Chicago Public Schools during the 2012-2013 school year, specifically for food-induced allergic reactions. METHODS District-issued epinephrine auto-injectors were distributed to all public and charter schools in Chicago prior to the start of the 2012-2013 school year. Data on their use were collected, and frequencies were computed in the autumn of 2013. RESULTS Thirty-eight district-issued epinephrine auto-injectors were administered during the inaugural year of the Chicago Public Schools initiative. Epinephrine auto-injectors were administered to students (92.1%) and school staff (7.9%). Most district-issued epinephrine auto-injectors were administered in elementary schools (63.2%) and on Chicago's North-Northwest Side (36.8%). More than half (55.0%) of all district-issued epinephrine auto-injectors were administered for first-time anaphylactic events. Food-induced reactions accounted for more than half (55.3%) of all reactions requiring epinephrine auto-injector use, whereas the trigger of more than one third (34.2%) of all reactions requiring the use of an epinephrine auto-injector remained unknown. CONCLUSIONS Chicago Public Schools is the first large, urban school district in the U.S. to develop and implement the District-Issued Emergency Epinephrine Initiative, which helped 38 students and staff avoid potential morbidity and mortality. The impact of this initiative during its first year underscores the need for stocking undesignated epinephrine in schools across the country.