Introduction: Azithromycin exhibits poor therapeutic efficacy in children with macrolideresistant Mycoplasma pneumoniae pneumonia (MPP). Clarithromycin is a potential alternative, yet real-world evidence remains scarce. Objectives: To analyze the therapeutic efficacy and hospitalization costs of clarithromycin in treatment-naive and azithromycintreated hospitalized MPP children. Methods: This single-center retrospective study involved hospitalized MPP children admitted to Tianjin Children's Hospital from December 2023 to December 2024. Clinical data including age, inflammatory and biochemical indices were extracted from the electronic medical record system. Duration of fever, hospitalization, hospitalization costs, proportion of glucocorticoid use and bronchoscopy during hospitalization were analyzed. Results: 15,047 children were included: 7180 received azithromycin (0.5-6 years: 3127; 6-18 years: 4053), 2454 received clarithromycin (0.5-6 years: 1434; 6-18 years: 1020). At baseline, IL-6 and IL-10 levels were higher in the clarithromycin group than in the azithromycin group. Compared with the azithromycin group, the clarithromycin group presented significantly shorter mean duration of hospitalization and lower mean hospitalization cost (0.5-6 years: 11,876.9±4310.2 vs 11,043.7±3428.0 Chinese yuan [CNY], p