OBJECTIVES: The objective of this study was to compare the cost-effectiveness of different disease-modifying therapies (DMTs) strategies for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: A Markov model was developed to assess the cost-effectiveness and incremental cost-effectiveness ratios (ICER) for different strategies of using DMTs from a US third-party payer perspective. The strategies were symptom management (SM) alone, SM in combination with one of the following: interferon beta-1a, natalizumab (after switching from interferon beta-1a), and alemtuzumab (after using interferon beta-1a then switching to natalizumab). The time horizon was 20 years. All costs were converted to 2014 US dollars. Different willingness-to-pay (WTP) thresholds per quality-adjusted life year (QALY) were considered in the analysis. One-way sensitivity analyses and probabilistic sensitivity analysis were conducted. RESULTS: Over 20 years, the total costs per patient were estimated at $161,136.60 for strategy 1 (SM alone), $551,650.66 for Strategy 2 (SM and interferon beta-1a), $703,463.60 for Strategy 3 (SM and natalizumab), and $668,806.50 for Strategy 4 (SM and alemtuzumab). The accumulated QALYs were 10.49, 10.66, 10.69, and 10.71 for each of the four strategies 1-4, respectively. The resulting ICERs were 2,297,141.53 comparing Strategy 2 to Strategy 1, 5,060,431.33 comparing Strategy 3 to Strategy 2 and -1,623,918.00, comparing Strategy 4 to Strategy 3. CONCLUSIONS: Strategy 1 (SM alone) was the cost-effective strategy for treatment of RRMS when compared to other strategies. More studies are needed to assess the cost and effectiveness of DMTs using in MS patients.