Background: Drug allergy is a subtype of Adverse Drug Reaction (ADR) mediated by the immunologic system. Extreme drug allergy is poorly known in children that contribute to hospitalization in our region. 
Objectives: This research aimed to study major drug hypersensitivity reactions in the north of Iran among the hospitalized children.
Methods: This cross-sectional study was conducted at Bou Ali Sina Hospital in the north of Iran. We analyzed the medical files of 140 children admitted to the hospital with drug allergies from 2014 to 2018. The inclusion criteria were based on the DRESS (drug reaction with eosinophilia and systemic symptoms) scoring system, and those who scored more than four were enrolled. Patients with incomplete medical charts were excluded. The sampling methodology was based on the consecutive census method.
Results: In the current study, 62 patients were females (44.29%), and 78 were males (55.71%). Ninety-six cases (68.57%) were children under five, and 44 cases (31.43%) were over five years old. Most ADRs were seen in patients from urban areas (58.57%) than in rural areas (41.43%). In 116 children (82.6%), maculopapular rashes were seen. Phenobarbital and cefalexin had the highest levels of drug reactions, including 85 persons (55.19%) and 18 persons (11.69%), respectively. Pruritus, fever, and scaling were the most common symptoms observed in the patients. The most commonly used treatment was antihistamines.
Conclusions: The most causative medication inducing ADR was phenobarbital. The maculopapular rash was the most common skin manifestation, and there were no relationships between sex, age, medication type, and type of hypersensitivity reactions.