Abstract Background Chronic spontaneous urticaria (CSU) is characterized by the repeated occurrence of persistent hives and/or angioedema for ≥6 weeks, without specific external stimuli. H 1 ‐antihistamines have long been the standard of care of CSU, but many patients remain uncontrolled even at 4× the approved dose. Add‐on therapy with omalizumab has proven effective in clinical trials, but little is known about omalizumab treatment in Belgium. Objective To collect real‐world clinical data on omalizumab treatment in adults with CSU in Belgium. Methods This was an observational, retrospective chart review of adults with CSU, who initiated omalizumab treatment between August 2014 and December 2016 (maximum 28 months follow‐up). Results In total, 235 patients were included (median time from symptom onset to diagnosis, 5.4 months; median time from diagnosis to commencing omalizumab, 6.7 months). Treatments used before/after commencing omalizumab did not always adhere to guidelines; many patients (26.4%/11.1%) received first‐generation H 1 ‐antihistamines, while 20.4% used omalizumab monotherapy after initiating treatment. The mean interval between omalizumab administrations was 4.8 (SD 1.7) weeks; 67.8% of patients had ≥1 interval prolongation and/or shortening. Mean baseline 7‐day Urticaria Activity Score (UAS7) was 32.0 (SD 6.05); this improved to 12.6 (SD 11.2) after 1 month of omalizumab. About 67.2% of patients reached UAS7 ≤ 6 (well controlled) during the study. A total of 87 patients stopped omalizumab and never restarted before the end of the observation period; the most prevalent reason was remission of symptoms (49.4% of patients), followed by lack of effect (12.6%), lost to follow‐up (6.9%) and adverse events (3.4%). Headache was the most common adverse event ( n = 8/82). No anaphylaxis was reported. Conclusions This study revealed that patients initiated on omalizumab in Belgium had severe CSU at baseline, and showed substantial improvements after 1 month of treatment. Greater adherence to the ...