OBJECTIVES: To determine cost-effectiveness of natalizumab compared with other disease-modifying therapies (DMT) for the treatment of relapsing-remitting multiple sclerosis (RRMS) in Russia. METHODS: Clinical and economical analysis was conducted using modeling (a decision tree model) and the "cost-effectiveness" method.  A model was based on assumptions about the effectiveness of the compared drugs derived from the Cochrane meta-analysis by Filippini G. et al. (2013). The information on the cost treatment information of RRMS was based on the Russian standards of care. Model inputs were drug acquisition costs (wholesale acquisition cost), costs of drug administration and monitoring, costs of treating relapses. The study time frame was 2 years. An annual discount rate of 5 % was applied to costs. RESULTS: The overall 2-year cost of therapy per patient was 75,088 USD (2,493,682 RUB)  for natalizumab (Tysabri), 47,187 USD (1,567,083 RUB) for intramuscular (IM) interferon beta-1a (Avonex), 47,075 USD (1,563,370 RUB) for subcutaneous (SC) interferon beta-1a (Rebif 44), 43,962 USD (1,459,976 RUB) for glatiramer acetate (Copaxone), and 39,826 USD (1,322,636 RUB) for interferon beta-1b (Betaferon). As a criterion of effectiveness  a relative risk reduction of one or more relapses over 24 months of treatment compared with placebo was chosen (42.8 % for natalizumab, 21.6% for glatiramer acetate, 15.2% SC interferon beta-1a, 10.5% for interferon beta-1b and 3.6% for IM interferon beta-1a). The cost per relapse avoided was lowest for natalizumab at 1,754 USD (58,264 RUB), followed by 2,035 USD (67,591 RUB) for  glatiramer acetate, 3,097 USD (102,853 RUB) for subcutaneous (SC) interferon beta-1a, 3,793 USD (125,965 RUB) for interferon beta-1b, and 13,108 USD (435,301 RUB) for intramuscular (IM) interferon beta-1a. CONCLUSIONS: Natalizumab was the most cost-effective therapy for RRMS as measured by total cost of treatment per relapse avoided.