OBJECTIVES To compare medication adherence to interferon beta (IFNβ)-1b and IFNβ-1a subcutaneous (SC) in patients with multiple sclerosis (MS). METHODS This was a retrospective analysis of patients with a diagnosis of MS in a national managed care database that had ≥1 outpatient DMD claim during the 7/1/2002 to 12/31/2005 selection period. Eligible patients were continuously enrolled for 6 months before and 24 months after their initial drug claim (index date) and were between 18 and 65 years of age. Medication possession ratios (MPRs) were calculated as the percentage of ambulatory days during the 24-month post-index period from the date of first use of the index DMD. The primary analysis was logistic regression predicting likelihood of adherence (MPR ≥85%) by treatment group (IFNβ-1b versus IFNβ-1a SC), including covariates of age, sex, and region of the country. RESULTS A total of 530 MS patients (IFNβ-1b, n=206, IFNβ-1a SC, n=324) met the study criteria. Patients had a mean age of 43.6 years, 77.2% were women, 49.0% were located in the Midwest, and 94.2% had commercial insurance. Average 2-year MPRs were 57.9% and 63.7% (P=0.020) for IFNβ-1b and IFNβ-1a SC, respectively. The percentage of patients who were adherent (MPR ≥85%) was 39.3% for IFNβ-1b vs 49.4% for IFNβ-1a SC. A logistic regression using categorical MPR as the dependent variable found that IFNβ-1a SC patients were significantly more likely to be adherent than IFNβ-1b patients (OR=1.603, P=0.0110). Older age (in 10 year increments) was also a significant predictor of adherence (OR=1.301, P=0.0037). Sex and region of the country were not statistically significant. CONCLUSIONS In this retrospective analysis, patients using IFNβ-1a SC were more likely to be adherent with their DMD therapy over a 2-year period than patients using IFNβ-1b, while controlling for age, sex, and region of the country.