BACKGROUND This prospective observational study aimed to evaluate the validity of appendicitis inflammatory response (AIR) score in differentiating advanced (perforated) from simple (non-perforated) appendicitis in pediatric patients. METHODS A single-center prospective cross-sectional study was conducted between 1 January 2019 until 1 May 2020 including 184 pediatric patients who underwent appendectomy. Based on the intraoperative finding of advanced (n = 38) or simple (n = 146) appendicitis the patients were divided into two groups. Recipient-operator curve (ROC), with calculation of sensitivity and specificity of best cutoff and the area under the curve (AUC), were used to measure the diagnostic value and the potential for risk stratification of the AIR score, among the patients with simple or advanced acute appendicitis. RESULTS The median value of the AIR score in the perforated and non-perforated groups was 10 (interquartile range, IQR 9, 11), and was 7 (IQR 6, 9), respectively (p < 0.001). Based on the calculated value of AIR score, the patients were classified with a high precision into low, indeterminate and high risk groups for acute appendicitis (p < 0.001). A cutoff value of ≥9 was demonstrated to serve as a reliable indicator of perforated appendicitis with a sensitivity and a specificity of 89.5% and 71.9%, respectively (AUC = 0.80; 95% CI: 0.719-0.871; p < 0.001). CONCLUSIONS Acute appendicitis can be detected with a high level of sensitivity and specificity using the AIR score. Also, the AIR score may differentiate perforated from non-perforated appendicitis in pediatric patients with a high level of accuracy.