OBJECTIVES: To determine cost-utility of interferons intramuscular beta-1-a (IFNβ-1a-IM), subcutaneous beta-1-a (IFNβ-1a-SC), subcutaneous beta-1-b (IFNβ-1b-SC) in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) in Colombia.  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 relapses during 24 months, survival rate at 20 years, Quality-Adjusted Life Years (QALYs). Direct costs were calculated for the year 2015. 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: The proportion of patients without relapses are: INFβ-1a-IM, 34.1%; INFβ-1a-SC, 23.9%; INFβ-1b-SC, 13.7%.  Most common complications include depression (53%), spasticity (49%) and fatigue (70%). Total discounted costs to 20 years are: no treatment, US$ 40,673; IFNβ-1a-IM, US$ 147,971; IFNβ-1a-SC, US$ 179,698; IFNβ-1b-SC, US$ 141,351. Discounted QALYs to 20 years in 1000 patients are: no treatment, 7,434; IFNβ-1a-IM, 9,078; IFNβ-1a-SC, 8,601; IFNβ-1b-SC, 8,104. ICER versus no treatment are: IFNβ-1a-IM, US$ 65,276; IFNβ-1a-SC, US$ 119,188; IFNβ-1b-SC, US$ 150,419. Survival rates to 20 years are: no treatment, 68.3%; IFNβ-1a-IM, 89.5%; IFNβ-1a-SC, 84.2%; IFNβ-1b-SC, 77.7%. With a willingness to pay higher than US$ 60,000, IFNβ-1a-IM has a probability higher than 80% to be the chosen treatment, for lower values, the highest probability is no treatment strategy. In the univariate sensitivity analysis, IFNβ-1a-IM is dominant over IFNβ-1a-SC in all scenarios of costs, and IFNβ-1a-IM is dominant over IFNβ-1b-SC consideringthe minimum cost.  CONCLUSIONS:  IFNβ-1a-IM is the most cost-effective strategy in patients with RRMS, both in terms of improved survival and long term QALYs as well as in terms of lowest ICER.