Adherence to disease-modifying therapies (DMTs) is essential for the reduction of multiple sclerosis (MS) progression and relapse. However, only limited data currently exist on the impact of treatment adherence on MS-related clinical and economic outcomes in the real world setting. To assess the impact of treatment adherence on MS-related hospitalizations (inpatient [INP]), ER visits, MS relapses, and medical costs. Patients with a parts per thousand yen1 ICD-9-CM code for MS who received a parts per thousand yen1 DMT between July 1, 2004 and June 30, 2008 were identified using the administrative claims database. The first DMT received during the study period was defined as the index treatment and a parts per thousand yen6-month preindex and a parts per thousand yen12-month postindex continuous health-plan enrollment were required for inclusion. Adherence was assessed using the medication possession ratio (MPR); patients with MPR a parts per thousand yen80% were regarded as adherent. Multivariate analyses were used to evaluate the impact of adherence on MS-related outcomes after controlling for baseline demographic and clinical characteristics. In this cohort (n=2446), 59.6% of the patients were adherent to their DMT. Compared with the nonadherent group, adherent patients were significantly less likely to have MS-related INP (odds ratio [OR]: 0.63, 95% confidence interval [CI], 0.47-0.83) and MS relapses (OR: 0.71, 95% CI, 0.59-0.85). No significant difference was found in ER risk between adherent and nonadherent groups (8.4% vs. 10.5%, P=0.068, OR: 0.80, 95% CI: 0.60-1.07). On average, the adherent group incurred lower medical costs than the nonadherent group ($3380, 95% CI, $3046-$3750 vs. $4348, 95% CI, $3828-$4940, P=0.003). Treatment adherence is associated with better clinical and economic outcomes including lower risks for MS-related hospitalization, MS relapse, and less MS-related medical costs. Treatments that require infrequent administrations and have favorable adherence profiles may benefit patients who are unable to adhere to DMT therapies. Such treatments may be important in improving disease outcomes and may be suitable therapeutic candidates for the management of MS.