BACKGROUND The management of anaphylaxis in pediatric emergency units (PEU) is sometimes deficient in terms of diagnosis, treatment, and subsequent follow-up. The aims of this study were to assess the efficiency of an updated protocol to improve medical performance, and to describe the incidence of anaphylaxis and the safety of epinephrine use in a PEU in a tertiary hospital. METHODS We performed a before-after comparative study with independent samples through review of the clinical histories of children aged <14 years old diagnosed with anaphylaxis in the PEU according to the criteria of the European Academy of Allergy and Clinical Immunology (EAACI). Two allergists and a pediatrician reviewed the discharge summaries codified according to the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) as urticaria, acute urticaria, angioedema, angioneurotic edema, unspecified allergy, and anaphylactic shock. Patients were divided into two groups according to the date of implantation of the protocol (2008): group A (2006-2007; the period before the introduction of the protocol) and group B (2008-2009; after the introduction of the protocol). We evaluated the incidence of anaphylaxis, epinephrine administration, prescription of self-injecting epinephrine (SIE), other drugs administered, the percentage of admissions and length of stay in the pediatric emergency observation area (PEOA), referrals to the allergy department, and the safety of epinephrine use. RESULTS During the 4 years of the study, 133,591 children were attended in the PEU, 1673 discharge summaries were reviewed, and 64 cases of anaphylaxis were identified. The incidence of anaphylaxis was 4.8 per 10,000 cases/year. After the introduction of the protocol, significant increases were observed in epinephrine administration (27% in group A and 57.6% in group B) (p = 0.012), in prescription of SIE (6.7% in group A and 54.5% in group B) (p = 0.005) and in the number of admissions to the PEOA (p = 0.003) and their duration (p = 0.005). Reductions were observed in the use of corticosteroid monotherapy (29% in group A, 3% in group B) (p = 0.005), and in patients discharged without follow-up instructions (69% in group A, 22% in group B) (p = 0.001). Thirty-three epinephrine doses were administered. Precordial palpitations were observed in one patient. CONCLUSIONS The application of the anaphylaxis protocol substantially improved the physicians' skills to manage this emergency in the PEU. Epinephrine administration showed no significant adverse effects.