OBJECTIVES: To assess cost effectiveness of Natalizumab, Glatiramer Acetate (GA) and Interferon-β in treating patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) from a United States (US) patient’s perspective. METHODS: A 30-year Markov model was developed with patients transitioning through health states based on the Kurtzke Expanded Disability Status Scale (EDSS). Patient health status was defined as mild, moderate, or severe when their EDSS score was 0.0-3.5, 4.0-6.0, 6.5-9.5, respectively. The model was parameterized with data from an extensive literature review and was adjusted where necessary to 2008 values. Transition probabilities included patients initial distribution based on EDSS score, relapse rate, mortality rate, and progression rate. The total cost included direct (inpatient and outpatient admissions, office visits to physicians, examinations, medication, medical devices, alterations to the care, and informal care from family) and indirect costs (productivity losses, and early retirement). The utility considered was Quality Adjusted Life-Year (QALY). Sensitivity analyses were conducted on all the transition probabilities at a range of ±25% to check the robustness of the result. RESULTS: Based on the result of the 30 year Markov Model, patients treated with Natalizumab spend $1,104,773 to gain 10.47 QALYs, while patients treated with Interferon- β spend $880,199 to obtain 9.88 QALYs and for those patients treated with GA have to pay $907,854 to yield 7.07 QALYs, which means patients treated with Natalizumab, Interferon- β or GA have to spend $105,517, $89,088, $128,409 respectively to gain one QALY. The model suggests that Interferon- β is the most cost-effective DMT agent, with an ICER of $380,634 per QALY compared with Natalizumab. Compared with GA, the ICER for Interferon- β per QALY was $9,841. Sensitivity analysis showed that the results were robust to changes in all parameters. CONCLUSIONS:  In our study, Interferon-β proved to be more cost effective than both Natalizumab and GA for RRMS patients.