Diagnostic guidelines for penicillin allergy in children recommend cumbersome protocols based partially on data from adults, which may be suboptimal for pediatric use. To assess the accuracy of tools for diagnosis of penicillin allergy in children. A prospective multicenter study was conducted in children with reported adverse events related to penicillin, excluding severe reactions. All patients underwent a uniform diagnostic protocol consisting of clinical history, skin tests, serum specific IgE, and, regardless of these results, drug provocation tests (DPT). 732 children (mean 5.5 years; 51.2% males) completed the allergy work-up, including DPT. Amoxicillin triggered 96.9% of all reactions. None of the patients with an immediate index reaction (IR) developed a reaction on DPT. Penicillin allergy was confirmed in 35 subjects (4.8%): 6(17%) immediate and 29(83%) non-immediate reactions in the DPT. No severe reactions were recorded. The allergist diagnosis based upon the clinical history was not associated with the final outcome at DPT. In 30 of 33(91%) allergic patients, all skin tests and sIgE were negative. A logistic regression model identified the following to be associated with PNC allergy (p3 days vs ≤24 hours (OR=8.96; 95% CI: 2.01-39.86), and IR while receiving corticosteroids (OR=2.68; 95% CI: 1.30-5.54). Conventional predictors of allergy to penicillin performed weakly. The authors propose straightforward penicillin provocation testing in controlled, experienced centers for the diagnosis of non-severe penicillin allergy in children. Copyright © 2018. Published by Elsevier Inc.