OBJECTIVES: The study examined determinants of prescription drug expenditures in patients with Multiple Sclerosis (MS) in United States (US). METHODS: Retrospective cross-sectional study was conducted using the 2002-2009 Medical Expenditure Panel Survey (MEPS) data, a nationally representative data on the community dwelling, non-institutionalized US population. The study sample included patients diagnosed with MS (ICD-9-CM: 340). Weighted descriptive statistics were performed to estimate the total and prescription drug expenditures. Multiple Ordinary Least Square regression analysis within the conceptual framework of Anderson Behavioral Model was performed to identify factors associated with prescription drug expenditures. The log transformation of the prescription drug expenditures was carried out to address skewed nature of cost data. RESULTS: An estimated of 4.1 million patients were diagnosed with MS during 2002-2009. The total average expenditure for MS patients was $17,619 (95% CI: 16,385-18,913). Of which 44% was attributable to the prescription drugs cost, i.e. $7760 (95% CI: 7169 – 8350). The linear regression revealed that predisposing (region), enabling (health insurance coverage) and need (charlson comorbidity score) factors were significantly associated with prescription drug expenditures. Patients from the Midwest region had 65% higher prescription expenditure than the west region patients. Patients with public insurance had 164% higher prescription expenditures than uninsured patients. One unit increase in charlson comorbidity score was associated with 28% higher prescription drug expenditure. CONCLUSIONS: The total prescription drug expenditures accounted for nearly half of total medical expenditure in patients with multiple sclerosis. In addition to need factors, the predisposing and enabling factors played an important role in influencing prescription drug expenditures in patients with multiple sclerosis.