Objective To explore the clinical efficacy and safety of omalizumab in the treatment of aspirin-aggravated respiratory diseases (AERD).Methods A retrospective analysis was performed on 32 AERD patients who received omalizumab in the department of otolaryngology, the first affiliated hospital of Chongqing medical university from January 2019 to April 2023. Visual analogue scale (VAS) score of nasal symptoms, nasal polyp score (NPS), sinus CT Lund-Mackay score (LMS), University of Pennsylvania olfactory recognition test (UPSIT) score, peripheral blood eosinophilic count, exhaled nitric oxide (FeNO), pulmonary function and adverse reactions, quality of life score before and after treatment were compared. Results After 24 weeks of omalizumab treatment, the VAS scores of runny nose and head and facial pain did not improve significantly, but the VAS scores of nasal congestion and anosmia decreased and the UPSIT scores increased significantly (P<0.05), suggesting the improvement of nasal symptoms. After treatment, NPS, LMS and 22-item sinonasal outcomes test (SNOT-22) scores were significantly decreased (P<0.05), indicating that sinus inflammation was obviously controlled and quality of life was improved. Pulmonary ventilation function improved, FeNO decreased and asthma control test (ACT) score increased, indicating significant improvement in lower airway inflammation control and symptoms (P<0.05). The absolute value of peripheral blood eosinophils decreased significantly (P<0.05). Incidence of adverse reaction of 270 injections was 0.3%, indicating good safety.Conclusion The application of omalizumab can effectively control the upper and lower airway inflammation of AERD and improve the quality of life of patients with reliable efficacy and good safety.