OBJECTIVES: Long-term treatment adherence of patients with multiple sclerosis (MS) treated with injectable drugs is a general concern. Closely monitoring patients’ therapy adherence may be beneficial. The objective of this study was to assess treatment adherence of MS patients treated with the injectable drug interferon beta-1a, administered with the RebiSmart system. METHODS: A retrospective observational study was conducted, monitoring patients’ treatment adherence with the RebiSmart system in their normal treatment setting. The RebiSmart is an electronic, multidose auto-self-injection device aimed to improve assessment of treatment adherence. It contains a cartridge including a weekly dose. The device can accurately record time and dosage of each administered injection. Patients can view their own dosing log. Moreover, patients’ physicians can download the information providing an objective record of treatment adherence. To determine treatment adherence with RebiSmart, anonymous patient-level data of Dutch and German patients were extracted from the RebiSmart systems on dosing, time, and number of administrations over a five-year time-period. Adherence was defined as taking >80% of the treatment doses according to the schedule the doctor prescribed. RESULTS: Data was collected from 1832 patients (81% German, 73% females, average age 40.1 years). In total, 95% of the cartridges were used completely, indicating low drug spillage. Over the complete observational period, 91% of all doses were administered according to doctor’s prescription. Examining individual adherence, 83% of the patients were considered adherent the whole period using interferon beta-1a. Results from Dutch and German patients were similar. CONCLUSIONS: Patients using the RebiSmart device in this study had a considerably higher adherence level than the approximately 60% adherence indicated by previous research studying adherence of MS patients on disease-modifying drugs. Drug spillage was low. Using an auto-injection device monitoring patients’ treatment behavior may positively contribute to treatment adherence. This should be further investigated in comparative research.