Objective: To examine the relationship between 3 measures of medication adherence for relapsing multiple sclerosis (MS)-related drug therapy and the likelihood of experiencing a severe MS relapse. Methods: Subjects were selected from the PHARMetrics database if they had at least 1 MS drug (Avonex®, Betaseron®, Copaxone®, Rebif®) claim from January 1, 2000 through December 31, 2004, were continuously eligible for 24 months after their first MS-related prescription (index date), and 6 months prior to the index date. Subjects were excluded if the were <18 or >65 years of age, exposed to Tysabri® after the index date, had evidence of study medication use in a healthcare facility, or if admitted to a long-term care facility. Severe MS relapse was defined as an MS-related hospitalization or emergency room visit. MS-related medication adherence was measured by 3 methods: medication possession ratio (MPR), consistence, and persistence. Covariates included, age, gender, region of the country, and treatment status (new or existing), comorbidities, and therapy type (mono- or multi-drug therapy). Results: Subjects (N=2388) had a mean age of 43.9 years, 76.7% were new patients, 8.1% had at least 1 severe MS relapse, and 76.4% were female. All 3 adherence measures were significantly associated with severe MS relapse with odds ratios of 0.921 (MPR), 0.946 (persistence), and 0.895 (consistence) indicating that increased adherence is associated with decreased likelihood of experiencing a severe MS relapse. Other significant covariates (p<0.05) in all models were comorbidity and East region (Mid West reference). Age, gender, and the other regions were not significant at alpha = 0.05. These results are consistent with previously reported findings on maximum gap in drug therapy and likelihood of a severe MS relapse. Conclusion: The relationship between MS-related drug therapy adherence and the reduced likelihood of a severe MS relapse is consistently supported across three measures of medication adherence.