Background: Adherence to Multiple Sclerosis (MS) treatment is considered one of the crucial factors for ensuring optimal clinical outcomes. Research has shown that the use of self-injector devices improves patient compliance with treatment. Therefore, the main purpose of this study is to evaluate the ease of use of RebiSmart (R) 2.0 in clinically isolated syndrome/relapsing-remitting MS patients during 12 months treatment period. Methods: A total number of 290 subjects entered into data collection; 249 (86%) of them completed the whole 12 months study period. The primary endpoints and the secondary endpoints were assessed by the User Study Questionnaire. Adherence data were retrieved from RebiSmart (R) 2.0 (Menu - Dose History) on the respective patient's visit. Outcome measures also included Expanded Disability Status Score, Kurtzke Functional Systems, and Modified Social Support Survey, Modified Social Support Survey-5. Results: This study demonstrated a very high proportion (>95%) of patients with a positive rating of the overall ease of use and the overall convenience of RebiSmart (R). The proportion of patients with a positive rating of the ease of use by individual domains and the functions of RebiSmart (R) were also high (>80%). Conclusion: The findings demonstrate a very good perception of the usability of the device by patients overall and in its individual functions.