BACKGROUND: Omalizumab is a preferred treatment in antihistamine-refractory chronic spontaneous urticaria (CSU) patients. However, factors that may impact treatment response remain to be explored. OBJECTIVE: This study aimed to examine the factors affecting treatment response in CSU patients receiving omalizumab. METHODS: This was a retrospective study that included 123 patients who received omalizumab treatment for CSU between January 2015 and April 2024. After administering omalizumab, we evaluated therapeutic efficacy with the urticaria control test (UCT). According to UCT, patients were classified as complete responders, partial responders, and nonresponders. RESULTS: The median age of the patients was 42 (31-50) years, and there were 77 (62.9%) female patients. Sixty-four (52%) patients exhibited complete response, and 43 (35%) patients exhibited partial response to omalizumab treatment, whereas 16 (13%) patients were nonresponders. Autoimmune disease (AID) was present in 31 (25.2%) patients. The most common AID was thyroid autoimmunity, seen in 24 (77.4%) patients. AID was significantly higher in omalizumab treatment nonresponders than in partial and complete responders. The presence of an autoimmune thyroid disease was an independent risk factor for failure to respond to omalizumab treatment. Baseline IgE levels were significantly higher in omalizumab treatment responders with a complete response compared to those with a partial response and nonresponders. CONCLUSION: Response to omalizumab treatment was influenced by the presence of an AID and baseline serum total IgE level. A concurrent autoimmune thyroid disease was found to be an independent risk factor affecting failed treatment response. Factors that can predict response to omalizumab treatment can help guide patients to more effective treatment.