Background Data are limited regarding the effectiveness of omalizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Our aim was to evaluate the clinical and functional effectiveness of omalizumab in patients with EGPA in long-term follow-up.Methods This study was a retrospective chart review of patients with EGPA who were treated with omalizumab injections between May 2012 and April 2018. Once treatment with omalizumab was started, data were collected at various time points: baseline, the 16th week, 1st year, and annually until the last evaluation.Results Eighteen patients (16F/2M) with a mean age of 48.61 ± 11.94 years were included. Data were available for all patients for the first year, 12 patients for the second year, 10 patients for the third year, 8 patients for the fourth year and 5 patients for the fifth year. All patients were on mean dosage of 15.77 ± 7.6 mg/day oral corticosteroid (OCS) as daily bases for mean 8.61 ± 4 years besides high-dose inhaler corticosteroid/long-acting beta agonist. Antineutrophil cytoplasmic antibodies (ANCA) were positive in 2 patients, and 8 patients were diagnosed as having vasculitis by skin biopsy, one patient had polyneuropathy, and one patient had cardiac involvement.By considering the individual responses of patients and the level of improvement at the last evalulation, 10 (55.6%) patients responded completely, 1 responded partially, and 7 (38.9%) had no improvement. Omalizumab worked as a steroid-sparing agent in all patients and the daily OCS dose was reduced with a mean dosage of 6.28 mg/day at the end of the first year. The mean OCS reduction time for the whole group was 4 months. A reduction in asthma exacerbations/hospitalizations, improvement in forced expiratory volume in 1 second, and no decrease in the eosinophil count during treatment with omalizumab were also observed.Conclusions Omalizumab improved asthma control in some patients with EGPA with uncontrolled asthma by reducing asthma exacerbations and oral steroid requirement. However, more data are needed before recommending widespread use of omalizumab in patients with EGPA.