OBJECTIVES To estimate total and disease-attributable costs and resource utilization associated with the use of disease-modifying therapies (DMTs) by multiple sclerosis (MS) patients from administrative claims data. METHODS Data from the HealthCore Integrated Research Database were used to identify patients with ≥1 medical claims for MS (ICD-9-CM code 340.xx). The date of first MS claim during January 1, 2004-March 31, 2007 was defined as the index date and patients were classified into 4 DMT treatment groups based on first DMT used during the post index period (i.e., intramuscular interferon beta-1a (IMIFb-1a), subcutaneous interferon beta-1a (SCIFb-1a), glatiramer acetate (GA), interferon beta-1b (IFb-1b)). All-cause and MS-attributable costs and resource utilization associated with inpatient hospitalizations, emergency room visits, physician office visits, other outpatient services and prescription drug claims were determined by DMT group. Baseline patient demographic characteristics and comorbidities were also determined. Annualized total and MS-attributable costs were analyzed using multivariate analysis to control for baseline differences between groups. RESULTS A total of 2703 MS patients (IMIFb-1a=950; SCIFb-1a=481; IFb-1b=378; GA=894) received DMTs during follow-up. Patient mean age was 43±10 years and 75% were female. The proportion of patients with ≥1 MS-attributable hospitalization differed between groups (p<0.01), ranging from 29.7% (IMIFb-1a) to 38.5% (SCIFb-1a). Unadjusted total annualized costs were lowest for IMIFb-1a, $21,457, and highest for SCIFb-1a, $26,201 (p<0.01), whereas unadjusted annualized MS-attributable costs were lowest for IMIFb-1a, $17,370, and highest for SCIFb-1a, $21,617 (p<0.01). After adjusting for baseline differences, total annualized costs were significantly higher for GA ($22,394, p=0.019), and SCIFb-1a ($24,526, p<0.0001) compared to IMIFb-1a ($21,130) while MS-attributable costs were significantly higher for SCIFb-1a ($20,942, p<0.0001) compared to IMIFb-1a ($17,295). CONCLUSIONS Total and MS-attributable costs were lowest for IMIFb-1a and highest for SCIFb-1a. Economic impact, in addition to outcomes from clinical studies, may be useful in understanding the overall benefits of different DMTs.