OBJECTIVES: To evaluate the economic outcomes of three kind of interferon-beta comparing to placebo: IM IFNb1-a, SC IFNb1-a, or SC IFNb1-b in patients diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS). METHODS: A literature-based Markov model was developed to assess the cost-effectiveness of three interferon-betas with placebo for managing a hypothetical cohort of patients diagnosed with RRMS in Iran. Health states were based on the Kurtzke Expanded Disability Status Scale (EDSS), a widely accepted scale for assessing Multiple sclerosis. Disease progression transition probabilities for symptom management were obtained from natural history studies. Treatment effects of the interferon-beta therapies were taken from related multicenter randomized controlled trials and their long term follow up for RRMS and Secondary progressive Multiple Sclerosis (SPMS). Transition probabilities were adjusted to account for treatment discontinuation and age and sex adjusted death rate. Transitions among health states occurred in 2-years cycles for fifteen cycles. Only medical direct cost has been considered for evaluation. RESULTS: The incremental cost per quality-adjusted life-year for IM IFNb1-a therapies is $474,819, and dominated for SC IFNb1-a, or SC IFNb1-b compared with placebo. The incremental cost per prevention of utility loss due to relapses is $144912, $117455, $185907, for IM IFNb1-a, SC IFNb1-a, or SC IFNb1-b respectively compared with placebo.  CONCLUSIONS: The Markov pharmacoeconomics model determined that SC IFNb1-a was the best strategy of the 3 interferon-beta therapies used to manage MS in term of relapse, however none of these medicines were cost-effective considering progression of disease and utilities or avoiding utility loss due to relapses.