OBJECTIVES: This study aims to assess the cost-utility of delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF), a new disease modifying therapy (DMTs), in treatment of patients with Relapsing-Remitting MS (RRMS) in Portugal. METHODS: A 1-year cycle Markov model based on the ScHARR MS Model was used to simulate disease progression, measured by Kurtzke Expanded Disability Status Scale (EDSS), relapses, and conversion to secondary-progressive MS (SPMS). It was assumed that patients could discontinue first line treatment (DMF or glatiramer acetate) and switch to a second line, but would stop any treatment after conversion to SPMS or progression to EDSS7. Clinical inputs for active treatments (disability progression, relapse rate and discontinuation of ITT population) were estimated on a mixed treatment comparison while natural history was based on DMF clinical trials and London Ontario database. Utility weights for patients and caregivers were derived from DMF clinical trials and the UK-MS Survey. Resource consumption by EDSS and due to relapses was based on published literature relevant to the Portuguese setting. Unit costs were obtained from official sources. The analysis was conducted from the societal perspective, assuming a time horizon of 50 years and a discount rate of 5%, for both costs and benefits. RESULTS: When compared to glatiramer acetate, DMF was associated with delay in progression and reduction in annualized relapse rate, resulting in a gain of 0.39 quality adjusted life years (QALYs), but implying a cost increase of 8.971 € . The incremental cost per QALY is thus 17.433 €. Sensitivity analysis shows that results are more sensitive to disability progression rate. CONCLUSIONS: The incremental cost effectiveness ratio of 17.433 € is considerably below the threshold usually accepted for financing medicines in Portugal (around 30.000 €/QALY). Dimethyl Fumarate should be seen as a cost-effective therapy for the Portuguese setting.