OBJECTIVES: Chronic spontaneous urticaria (CSU) is a skin disease, with itchy hives that last for at least 6 weeks without an obvious external trigger. Omalizumab has been shown to diminish clinical symptoms and signs. The objective of this study was to determine the cost-effectiveness of omalizumab relative to cyclosporine and standard of care (up to 4 times the daily dose of H1-antihistaminics) for the Netherlands. METHODS: A Markov model was used in this study. The model’s settings and characteristics of the Dutch patient population were based on an online survey among clinical experts. These values were validated during a clinical expert committee meeting. The GLACIAL trial was used to describe transition probabilities. Data on health care consumption, quality of life and productivity losses were derived from medical records and a survey among 93 Dutch CSU patients. Health care consumption was valued using prices from the Dutch costing manual. Utilities were derived from EQ-5D and calculated using Dutch tariffs. Productivity losses were valued using Dutch wage rates. Comparator treatments were cyclosporine and standard of care. Uncertainty was assessed by one-way sensitivity analyses and probabilistic sensitivity analyses. RESULTS: Omalizumab was more effective than cyclosporine (incremental QALYs: 11.3). Incremental costs for omalizumab were €51.052, resulting in an ICER of €4.510 per QALY gained. Compared to standard of care, incremental QALYs for omalizumab were 9.2 and incremental costs were €161.342 (ICER of €17.502/QALY gained). Productivity costs played an important role in the value of the ICER. Probabilistic sensitivity analyses resembled the results from the deterministic analyses. CONCLUSIONS: Omalizumab is cost-effective compared to both cyclosporine and standard of care. The ICER is well below the implicit cost-effectiveness threshold in the Netherlands, which ranges from €20.000-80.000 per QALY.