OBJECTIVES: Multiple sclerosis (MS) is a neurologic disease that can dramatically affect patients. The aim of this study is to conduct a cost-effectiveness analysis of natalizumab (Tysabri®) versus glatiramer acetate (Copaxone®) for treatment of Relapsing Remitting Multiple Sclerosis (RRMS) patients from the Brazilian Public Healthcare System (SUS) perspective.  METHODS: A Markov model with a 20-year time horizon comparing natalizumab to glatiramer acetate was developed. Health states were based on EDSS and relapses (moderate or severe). We obtained relapse and disability progression transition probabilities from natural history studies on RRMS patients. In each monthly cycle, patients can discontinue treatment, remain stable, progress to higher MS EDSS state, experience Progressive Multifocal Leukoencephalopathy (PML) or die.  Patients with EDSS score ≥ 7.5 receive best supportive care. Resource use and costs were validated by an expert’s panel and valued using Brazilian public official lists (DATASUS and BPS). Costs and outcomes (5%) were discounted. Probabilistic sensitivity analyses (PSA) covered variability in efficacy and costs. RESULTS: Use of natalizumab was associated with slower EDSS progression and reduced relapse burden. The life years gained (LYG) with natalizumab and glatiramer acetate was 10.65 and 10.09, respectively. Costs associated with natalizumab were USD 119.330 and USD 102.275 for glatiramer acetate. Incremental cost-effectiveness rate for natalizumab versus glatiramer acetate was USD 30.251/LYG. PSA has confirmed the consistency of base case results. CONCLUSIONS: For a patient with RRMS, this model shows that natalizumab was cost-effective when compared to treatment with glatiramer acetate, assuming the threshold of USD 50.000/LYG commonly mentioned by the Ministry of Health in Brazil.