In recent years, early use of highly effective disease modifying immunotherapies in relapsing-remitting multiple sclerosis (RRMS) demonstrated superior efficacy in preventing disability progression. For this study, we investigated ocrelizumab as first line therapy of RRMS in a monocentric, retrospective study. In our outpatient clinic, ocrelizumab was administered as first-line therapy in 33 patients with an anticipated highly active disease course. Patients were re-evaluated clinically every 6 months and at least annually with cranial magnetic resonance imaging (MRI), with a mean follow-up period of 27 months. Subgroup analyses were conducted based on age, sex, disease duration, and disability as measured by EDSS at initiation of therapy. Ocrelizumab therapy was administered within the first year of diagnosis. The median EDSS at the time of ocrelizumab initiation was 2.5, with male patients showing higher disability compared to the females. The annualized relapse rate (ARR) decreased from 2.24 to 0.058 during the observation period. EDSS remained stable throughout the therapy period for the entire cohort. Starting treatment earlier and at a lower initial EDSS correlated with a better outcome. Gender and age had no impact on the therapeutic efficacy. The most common infusion related reactions included fatigue (25 %) and headaches (9 %). Mild infections occurred in 21 % of patients. These data highlight the role of ocrelizumab as an effective first-line therapeutic approach for patients with highly active RRMS.