Abstract Background Up to 10% of children are labelled as penicillin allergic, requiring the use of suboptimal antibiotics as an alternative. In these children, a low-risk oral challenge with amoxicillin can be done to evaluate the accuracy of this allergy. An oral challenge pre-written order was implemented in our institution’s emergency department (ED). Objectives The aim of this study was to assess the success of the amoxicillin oral challenges in children labelled penicillin allergic in the ED. Design/Methods This is an ongoing prospective observational study conducted at a tertiary care paediatric hospital. Children considered at low risk of penicillin allergy (https://www.inesss.qc.ca/fileadmin/doc/INESSS/Rapports/Medicaments/Outil_aide-decision_allergies-EN_VF.pdf) and requiring amoxicillin according to the ED physician were prescribed an amoxicillin challenge according to a pre-written order set. In the absence of a reaction, patients were discharged with an amoxicillin prescription. Parents were contacted one month after the challenge to assess for late-onset reactions. Results Since June 2021, 70 children (24 female) underwent an amoxicillin challenge in the ED (Figure 1). The patients’ median age was 1 yo (6 months–12 yo). The most frequent discharge diagnoses in the ED were otitis media (65%) and pneumonia (24%). The challenge was successful in the ED for 69/70 (99%) patients. Sixty-two (89%) patients were successfully contacted for a follow-up phone call. Among them, 55/62 (89%) did not present any reaction. In total, 7/62 (11%) of the children had a reported reaction, one (1%) child had an immediate reaction to the challenge in the ED, while 6/62 (10%) had a rash appearing 1 to 61 days after the first dose of antibiotics. No severe reactions were reported by the parents after discharge from the ED. A correlation between the amoxicillin administration and the delayed reaction was considered less likely for 3/6 patients because of the later onset of symptoms (28-61 days). The three other patients were considered not to have a penicillin allergy after formal assessment at the allergy clinic. Conclusion Using a standardized pre-written order set for an amoxicillin challenge in the ED allowed 99% of participating children to be discharged safely with an amoxicillin prescription. Despite 10% presenting a rash after discharge, none were considered to have a late-onset reaction. This removed safely and rapidly the label of “penicillin allergy” from those paediatric ED patients, allowing optimal first-line antibiotics. It also eliminates the need for a consultation with an allergist in the majority of patients.