Omalizumab is an effective and safe treatment option with licensed doses in patients with chronic spontaneous urticaria (CSU); however, some patients are not responsive to licensed doses and require updosing. As studies concerning updosing were insufficient, the present study evaluated the effectiveness and safety of omalizumab updosing (300 mg every 2 weeks) in CSU patients. Data of CSU patients treated with omalizumab were analyzed retrospectively. As an outcome measure, physician assessment of treatment response (complete response [CR], partial response, and unresponsiveness) was used. In all, 49 patients depicting CR to omalizumab 300 mg every 4 weeks and 54 patients treated with omalizumab 300 mg every 2 weeks were included in the study. Mean duration of the disease in updosing group was significantly lengthier than the CR group. The mean percentage level of eosinophils and basophils was significantly higher in the CR group. The history of systemic corticosteroid and oral cyclosporine treatment was significantly more frequent in the updosing group. Treatment with omalizumab 300 mg every 2 weeks for 12 weeks led to CR in 41 patients (75.9%). Our results confirmed the efficacy and safety of omalizumab updosing. Low baso-phil and eosinophil levels could also be important factors in defining the need for updosing.