OBJECTIVES: To compare adherence rates, defined as the Medication Possession Ratio (MPR), for patients using alternative disease modifying therapies (DMTs) to treat multiple sclerosis (MS) that are enrolled in either a commercial insurance plan or through the Part D Medicare beneficiary program.   METHODS: Study patients had >1 pharmacy DMT claim [interferon, glatiramer acetate (GA), fingolimod or natalizumab] and  were enrolled in either a commercial health plan or Part D program between the dates of January 2010 and October 2012 for patients using interferon, GA and natalizumab and between the dates of October 2010 and October 2012 for patients using fingolimod. Mean monthly MPR rates were calculated as the percentage of time the patient had access to a specific medication.   RESULTS: The MPR for 243,330 and 197,784 commercial and Part D beneficiaries, respectively, were calculated across the study period. Adherence rates for commercial enrollees were similar across disease modifying therapies ranging from 75.4% for a once daily oral therapy to 79% for natalizumab. However, adherence in Medicare Part D beneficiaries was consistently lower than patients enrolled in commercial plans ranging from a reduction in MPR of 0.27% for GA to 7.4% in patients taking once daily oral fingolimod treatment.     CONCLUSIONS: Medicare Part D beneficiaries had lower rates of adherence compared to MS patient enrolled in commercial plans which could present a unique opportunity for medication management programs offered either through pharmaceutical companies, health plans or specialty pharmacies.