Abstract: Objective To investigate the efficacy and safety of azithromycin in children with moderate to severe bronchiolitis. Methods A total of 75 children with moderate to severe bronchiolitis hospitalized in the department of pediatrics of the First Affiliated Hospital of Bengbu Medical College from August 2017 to April 2018 were selected and divided into azithromycin intervention group (37 cases) and routine treatment group (38 cases) by random number table method. The routine treatment group was given routine treatment such as antiviral, budesonide combined with salbutamol atomization inhalation. The azithromycin intervention group was treated with azithromycin dry suspension [10 mg/ (kg·d)] for 3 days on the basis of the routine treatment in control group. The clinical criticality (CS) scores of the two groups were compared. The time of cough, wheezing, three concave sign and rale disappearance in lung, hospitalization time, and the adverse events such as neutropenia, thrombocytopenia, gastrointestinal symptoms, arrhythmia of heart rate and liver damage, were compared between the two groups. Results There were significant differences in CS scores before and after treatment between two groups (F=139.111, 158.341, all P<0.001). The CS score of the routine treatment group was significantly higher than that of the azithromycin intervention group (F=7.008, P=0.010). The cough, wheezing, triple concave sign, lung rale disappearance time and hospitalization time in the azithromycin intervention group were shorter than those in the routine treatment group (all P<0.05). There was no significant difference between the two groups in the occurrence of adverse events, such as liver damage, gastrointestinal symptoms and arrhythmia (all P>0.05). Conclusion Azithromycin is safe for the treatment of bronchiolitis, which significantly improve the symptoms and signs of children with bronchiolitis, shorten the course of disease, and can be applied in clinic.