OBJECTIVES: To assess the cost-effectiveness of natalizumab in patients with highly active relapsing/remitting multiple sclerosis (RRMS) in Mexico METHODS: A decision analytic model was developed based on the Kurtzke EDSS scale to estimate the incremental cost per relapse avoided with natalizumab from the Mexican Public Healthcare System perspective. Five-year costs of treating patients with MS included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided (data from AFFIRM for natalizumab and meta-analysis for interferon and glatiramer acetate [GA]). Costs and effects were discounted at 5% annually. One-way sensitivity analyses were conducted to assess uncertainty.  RESULTS: Mean 5-year estimated treatment costs were US$103,680 (natalizumab), US$78,980 (GA), US$67,045 (GA after mitoxantrone induction) and US$125,204 (interferon plus GA). Patients receiving natalizumab resulted in 1.04 expected relapses vs 6.47 for GA and 3.55 for interferon plus GA. Natalizumab dominated interferon plus GA in the incremental cost-effectiveness analysis, as it was less costly and more effective in reducing relapses. ICER for natalizumab vs GA was US$4,548 per relapse avoided and vs GA after mitoxantrone induction was US$6,745. One-way sensitivity analysis showed the results of the model were robust to changes in drug acquisition costs, administration costs, and costs of treating MS relapses. CONCLUSIONS: Natalizumab is a cost-effective therapy for Mexican patients with highly active RRMS. If natalizumab were used instead of interferon plus GA the public healthcare system would obtain savings.