Anaphylaxis is a potentially life-threatening, rapid-onset hypersensitive reaction, usually treated in the emergency department (ED). Failure to recognize anaphylaxis leads to under-treatment with epinephrine and even when correctly diagnosed, epinephrine is not always administered. In addition, often patients who are treated in the ED are not referred for allergy work-up. Simulation is a tool that increases exposure to events in a safe environment, allowing trainers to develop skills without harming patients. The main purpose of our study was to determine whether in situ simulation training increases the frequency of epinephrine use. The secondary aim was to observe whether simulation modifies the number of children investigated over the years before and after the setting up of the simulation training. All patients with anaphylaxis referred to the Pediatric Emergency Department (PED) of the Anna Meyer Children's Hospital from 2004 to 2010 [pre-simulation (PRE-s) period], and from 2011 to 2016 [post-simulation (POST-s) period], were retrospectively included in this observational study. Simulation was carried out using a high-fidelity patient simulator mannequin (SimBaby, Laerdal Medical, Inc, Stavanger, NY). The diagnosis of anaphylaxis was based on the EAACI guidelines. The use of epinephrine significantly increased (p < 0.05) between the PRE-s and POST-s time periods: 2.4% versus 10% patients, respectively. During the two time periods, we also observed a significant increase (p = 0.011) in the number of patients who underwent a complete allergy work-up: 36% versus 51% patients, respectively. According to our results, the in situ simulation program improved the correct management of anaphylaxis in terms of prompt use of epinephrine, and it also led to a higher number of patients being referred to the allergy unit for evaluation.