OBJECTIVES: To assess the cost-effectiveness of the Disease Modifying Treatments (DMT), Glatiramer Acetate (GA) and Interferon beta-1a (IFN) in monotherapy alone and in combination for the prevention of relapses with established Relapsing–Remitting Multiple Sclerosis (RRMS) among Spanish patients aged between 18 and 60 years old. METHODS: A Markov model was developed to represent the transition of a cohort of patients over a 10 year period using the perspective of the Spanish National Health Service (NHS). The model considered five different health states with one-year cycles including without relapse, patients with suspect, non-protocol defined and protocol defined exacerbations, as well as the category information lost. Efficacy data was obtained from the 3-year CombiRx Study. Costs were reported in 2013 Euros and a 3%discount rate was applied for health and benefits. Deterministic results were presented as the annual treatment cost for the number of relapses. A probabilistic sensitivity analysis was performed to test the robustness of the model. RESULTS: Deterministic results showed that the expected cost per patient was lower when treated with GA (€13,843) compared with IFN (€15,589) and the combined treatment with IFN+GA (€21,539). The number of relapses were lower in the GA cohort with 3.81 versus 4.08 in the IFN cohort and 4.18 in the cohort treated with IFN+GA. Results from probabilistic sensitivity analysis showed that GA has a higher probability of being cost-effective than the treatment with IFN or IFN+GA for threshold values from €28,000 onwards, independent of the maximum that the Spanish NHS is willing to pay for avoiding relapses. CONCLUSIONS: GA showed to be a cost-effective treatment option for the prevention of relapses in Spanish patients diagnosed with RRMS. When GA in monotherapy is compared with INF in monotherapy and IFN+GA combined, it may be concluded that the first is a dominant strategy.