OBJECTIVES: To assess the cost-effectiveness of delayed-release dimethyl fumarate (DMF) versus treatments for relapsing remitting multiple sclerosis (RRMS) from a Spanish Health System perspective. METHODS: A decision analytic Markov model was developed to assess the cost-effectiveness of DMF versus IFN beta (IFNβ)-1a IM, IFNβ-1a 22 and 44 mcg SC, IFNβ-1b SC, glatiramer acetate (GA) SC, teriflunomide, fingolimod and natalizumab in RRMS patients. Based on the Expanded Disability Status Scale (EDSS), 21 health states were defined (EDSS 0-9 RRMS, EDSS 0-9 SPMS and death). Disability disease progression rate, relapse rate, treatment disutility, adverse events, rates of withdrawal and disease related mortality were assessed over a 30-year period. Data sources included published literature, clinical trials, Spanish price/tariff lists, and national population statistics. Results are presented as quality-adjusted life-years (QALY) and incremental cost effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses were performed. RESULTS: DMF showed higher QALYs and lower costs compared to IFNβ-1a IM (0.122 QALYs; -2,761€), IFNβ-1a 44mcg SC (0.093 QALYs; -8,827€), IFNβ-1b SC (0.286 QALYs; -7,108€), GA SC (0.235 QALYs; -1,040€), teriflunomide (0.125 QALYs; -260€) and fingolimod (0.184 QALYs; -29,813€). In the comparison of DMF vs IFNβ-1a 22 mcg SC, DMF provided incremental QALYs of 0.193 and an anticipated ICER of 23,482€. Compared to natalizumab, DMF showed incremental QALYs of -0.143 and incremental costs of -29.001€, being less effective and cheaper Sensitivity analyses demonstrated the robustness of the model. At a decision-maker’s willingness to pay of < 30.000€, DMF was cost-effective in more than 80% of simulations versus IFN beta-1a IM, IFNβ-1a 44 mcg SC, IFNIβ-1b SC and GA SC; in 52% of simulations versus INFβ-1a 22 mcg SC; in 65% of simulations versus teriflunomide; and in 100% of simulations versus fingolimod. CONCLUSIONS: In this analysis DMF showed dominance in ICER against IFNβ-1a IM, IFNβ-1a 44 mcg SC, IFNβ-1b SC, GA SC, teriflunomide and fingolimod.