Background: Beta-lactam allergy is overdiagnosed. Diagnosis of penicillin allergy has been associated with a greater use of hospital resources and an increased risk of antibiotic-resistant infections, although this issue remains poorly studied in children. We aimed to compare patient characteristics and use of hospital resources in hospitalized children with and without a record of penicillin allergy. Methods: We identified all hospitalizations in children labelled as being allergic to penicillin in a database containing all hospitalizations in Portuguese public hospitals between 2000 and 2014, and compared these with a similar number of age-, sex-, and main diagnosis-matched hospitalizations without a penicillin allergy label. Comparisons were made for length of hospital stay, comorbidities (Charlson Comorbidity Index), in-hospital mortality, and hospitalization costs. Results: We identified 1,718 hospitalizations corresponding to children labelled as penicillin-allergic. Compared with patients without such a label, these children had longer hospital stays (mean 5 vs. 4 days, p = 0.03) and a higher comorbidity index (mean 0.11 vs. 0.09, p < 0.001). Hospitalization costs were also higher (EUR 2,071 vs. 1,798), but the difference was not significant (p = 0.12). Conclusions: Hospitalizations of children labelled as allergic to penicillin are associated with longer hospital stays, more comorbidities, and a tendency towards higher hospitalization costs. An accurate diagnosis of penicillin allergy based on clinical history and confirmatory tests is therefore essential in all paediatric patients.