OBJECTIVES: To determine cost-utility of dimethyl fumarate versus fingolimod, teriflunomide and no treatment in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) in Colombia (South America). METHODS: The base case patient has a RRMS severity < 2.5 according to Expanded Disability Status Scale, the perspective of analysis was from Colombian health system. Time horizon was 20 years; the annual discount rate was 5% for benefits and costs. Outcomes: proportion of patients without relapsing during 24 months, survival rate at 20 years, Quality-Adjusted Life Years (QALYs). Direct costs were calculated for the year 2017. A Markov decision model was constructed in a hypothetical cohort of 1000 patients, considering ten disease’ states. The model represents the probabilities of moving from state to state, leaving the treatment and dying. RESULTS: Clinical efficacies are: dimethyl-fumarate, 36%; fingolimod, 28%; teriflunomide, 12%. Most common complications include depression (53%), spasticity (49%) and fatigue (70%). Total discounted costs to 20 years are: no treatment, US$ 46,113; dimethyl-fumarate, US$ 372,421; fingolimod, US$ 341,324; teriflunomide, US$ 227,901. Discounted QALYs to 20 years in 1000 patients are: no treatment, 7,435; dimethyl-fumarate, 9,161; fingolimod, 8,792; teriflunomide, 8,016. ICER versus no treatment are: dimethyl-fumarate, US$ 189,040; fingolimod, US$ 217,426; teriflunemide, US$ 312,647. Survival rates to 20 years are: no treatment, 68.3%; dimethyl-fumarate, 90.2%; fingolimod, 86.4%; teriflunemide, 76.5%. To willingness to pay higher than US$ 195,000, dimethyl-fumarate has the highest probability to be the chosen treatment, for lower values, the highest probability is no treatment strategy. In the univariate sensitivity analysis, the dimethyl-fumarate case base ICER is lower than US$ 130,000 versus fingolimod and teriflunomide, according to the value reported in the willingness to pay curves. CONCLUSIONS: Dimethyl fumarate is the most cost-effective strategy in patients with RMSS, both in terms of improved survival and long term QALYs as well as in terms of lowest ICER.