OBJECTIVES: Omalizumab is a monoclonal antibody indicated for treatment of severe persistent allergic asthma inadequately controlled despite an optimal controller therapy. The purpose of this study is to determine a cost-effectiveness analysis of omalizumab vs ST in the treatment of severe asthma in Mexico. METHODS: A cost-effectiveness analysis was performed based on a six-state Markov model. The transition probabilities and the response rate were obtained from a meta-analysis. The pattern of resource use was derived from the Second Mexican Consensus of Asthma (steps 4 and 5). Unit costs of resources and medications were obtained from medical care in IMSS 2004, and were transformed to current prices using inflation rates. The cost of omalizumab was provided by the laboratory. The time horizon was one year. A discount rate was not required. The model was calibrated. The effectiveness rate was the number of days free from exacerbations. A one-way and two-way probabilistic sensitivity analysis was used using a Tornado chart. A stochastic optimization analysis was performed with 500 runs involving 100,000 Monte Carlo iterations; the budget and percent use of omalizumab were the model restrictions. Maximization of incremental net benefits was obtained with the model. RESULTS: The expected cost per patient was $14,940 USD (± $502) with omalizumab, while this figure was $6,144 USD (± $207) for ST. The expected effectiveness was 333 (±3) and 306 (±6) days without exacerbation/year, respectively. The stochastic optimization maximized the net incremental benefits with a ratio of 42% for omalizumab, and 58% for the standard therapy. The sensitivity analysis was robust in the conclusions of the basic study. CONCLUSION: Omalizumab is a cost-effective therapy in the management of patients with severe asthma. The ratio for omalizumab acquisition with stochastic optimization was 42%.