OBJECTIVES: To evaluate the cost-effectiveness analysis of two Disease-modifying drugs (DMD) used as first-line treatment of Relapsing Remitting Multiple Sclerosis (RRMS): interferon IFNβ-1a IM injection (Avonex®) and IFN β-1b SC injection (Betaferon®) from Iranian Ministry of Health perspective. METHODS: A cost-effectiveness analysis (CEA) was performed from Ministry of Health (MoH). The outcome of interest was number of relapses avoided. Costs were reported in 2011 USD. Costs and outcomes were discounted at 5%. The time horizon was two years. All uncertainties were tested via one-way sensitivity analyses. RESULTS: Total costs per patient over the time horizon of a study were estimated at 39923, 47670 and 52045 USD for symptom management, IM IFNβ-1a and SC IFNβ-1b, respectively. The incremental cost per relapse avoided was 25823 and 14965 USD for IM IFNβ-1a and SC IFNβ-1b, respectively, compared with no active treatment (symptom management). Results were sensitive to the discount rate, frequency of relapse and cost of DMDs. CONCLUSIONS: The cost-effectiveness analysis determined that INFβ-1b SC (Betaferon® ) was the best strategy of the two immunomodulatory therapies used to treatment of patients experiencing an relapsing-remitting  multiple sclerosis (RRMS) and resulted in better outcomes than symptom management alone. Sensitivity analyses indicated that the model was sensitive to changes in a number of key parameters, and thus changes in these key parameters would likely influence the estimated cost-effectiveness results.