OBJECTIVES: The objective of this study is to conduct a health economic evaluation and compare the health care costs associated with patients diagnosed with relapsing remitting multiple sclerosis and taking orally or subcutaneously administered disease modifying therapies (DMTs). METHODS: A large US administrative retrospective claims database was used to identify patients diagnosed with RRMS and were prescribed either orally or subcutaneously administered DMTs between January 2010 and December 2012 were included in the study. All patients were ≥ 18 years of age and continuously enrolled in the same health plan at least a year. Descriptive statistics, chi-square tests and logistic regression analysis were performed on the data and statistical significance level was set a priori at 0.05. RESULTS: There were a total of 3,216 patients on Orals and 10,507 on Subcutaneous DMTs that met study criteria. Patients on average were charged $5120.54±2356.75 and $3966.75±1904.01 for their treatment with Orals and Subcutaneous DMTs (p<0.001). However, the amount allowed (p<0.001) by the health plan was $4966.70±2336.18 and $3615.94±1752.21 and the actual amount paid (p<0.001) was $4860.56±2328.56 and $3504.89±1745.19 for a month supply. The annual cost of treating patients with Orals was higher than Subcutaneous DMTs ($61,446.57±28281.09 vs $47,601.01±22848.23, p<0.001). The majority of the Orals were charged anywhere between $50K and $100K (53.1% vs 11.9%, p<0.001) and Subcutaneous were charged between $25K and $50K (36.1% vs 80.4%) for their annual treatment. The mean cost of DMTs per day of treatment is higher for Orals compared to Subcutaneous ($151.04±21.25 vs $117.93±35.24, p<0.001). The logistic regression analysis showed that patients receiving Orals were eight times more likely to have costs for their treatment more than $50K per year compared to subcutaneous DMTs (OR 8.0, p<0.001).  CONCLUSIONS: Patients on Orals DMTs have a higher treatment costs than Subcutaneous administered DMTs.