OBJECTIVES: Disease-modifying drugs (DMDs) are a significant expenditure for treating multiple sclerosis. However, assessment of the cost-utility of DMDs compared with symptom management in the presence of long-term data has been limited. To assess the lifetime cost-utility from the Iranian healthcare perspectives of 4 disease-modifying drugs relative to symptom management alone in patients with relapsing-remitting multiple sclerosis using evidence from long-term published studies. METHODS: A Markov model was developed with patients transitioning through health states based on Kurtzke expanded disability status scale (EDSS). Patient costs included drug costs, other medical and lost worker productivity costs. Patient quality of life was considered in the form of utilities. Costs were valued in 2011 USD, and costs were discounted at 7.2%per annum. Various parameters and assumptions were tested in sensitivity analyses. RESULTS: Total costs per patient over the time horizon of a patient’s lifetime were estimated at 20285, 144194, 299279, 251255 and 69796 USD for symptom management, Avonex, Betaferon, Rebif and CinnoVex, respectively. As a result, the incremental cost per QALY for patients receiving Avonex, Betaferon, Rebif and CinnoVex was 607397, 1374355, 1166515 and 1010429 USD, respectively, when compared with symptom management. The results were sensitive to changes in time horizon, disease progression and drug costs. CONCLUSIONS: DMDs in RRMS patients is associated with increased benefits compared with symptom management, albeit at higher costs. Because patients receiving Avonex incurred slightly higher QALYs than patients receiving other DMDs, treatment with Avonex dominate other DMDs in Iran.