Background: Limited information is available on the use of omalizumab (OMA) updosing since its introduction as a second-line therapy in chronic spontaneous urticaria (CSU) in 2014. Practical guidelines from health authorities are lacking, and the specific characteristics of patients requiring higher doses remain unknown. Our objectives were to characterize the patterns of OMA updosing (defined as changes in dose and/or injection intervals), to identify the predictive factors associated with updosing, and to improve CSU management. Methods: We conducted a prospective, multicentric, real-life, observational study, including patients diagnosed with CSU and starting OMA. The data were collected at 0, 3, 6 and 9 months. The primary endpoint was the frequency of OMA updosing at 3 months. The secondary endpoints included an analysis of updosed patients’ profile, and an assessment of OMA efficacy and safety. Results: We included 153 patients. Twenty percent of patients at M3 were updosed, and 27% in total during the 9-month follow-up. Practitioners mainly chose to increase the frequency of injections (66%). At baseline, the updosed patients were more likely, to have inducible urticaria (50% vs. 33%, p=0.046), more severe CSU (UCT 3 vs. 4, p<0.001; DLQI 14 vs. 11, p=0.040), a lower lymphocyte count (1894 vs. 2100, p=0.026) and IgE below 70 UI/mL (65% vs. 45%, p=0.039). The side effects of OMA were not more frequent after updosing. Conclusion: One in five patient underwent updosing within just three months. OMA updosing is frequent in particular in cases of severe disease, inducible urticaria and low IgE blood levels.