Background: Ocrelizumab (OCR) is a B-Cell depleting humanized monoclonal antibody FDA-approved for treatment of relapsing remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). In the pivotal trials for both RRMS and PPMS, patients >55 years old were excluded. In clinical practice, many patients receive OCR therapy beyond this age cutoff. Here, we report on our single center cohort experience in this subset of patients. Objectives: To assess clinical and laboratory features in MS patients older than 55 years old treated with OCR as well as reason for OCR discontinuation, if applicable. Methods: Retrospective analysis of all OCR-treated patients infused at the University of Washington MS Centers infusion suite from March 2017 to October 2020. Patients >55 years old were included in the analysis. Chart review included clinic notes, emergency room visits, admissions, outside hospital encounters, and internal and external laboratory results available. Additionally, the EPIC search feature was used for the following key words: infection, UTI, urinary tract infection, PNA, pneumonia, URI, influenza, flu, cellulitis, sinusitis. Results: A total of 335 patients received OCR at our center, of whom 59 (17.6%) were above the age of 55 (range 56 84, 30 [50.8%] were 56 60 years old, 12 [20.3%] were 61 65, 10 [16.9%] were 66 70, 7 [11.9%] were >70). 28 (47.5%) were female. 14 patients discontinued OCR treatment during the time period reviewed. This was due to MS progression (n=5), repeated or severe infections (n=5) including one patient with a fatal infection (pneumonia), risk/benefit ratio (n=2), worsening psoriasis (n=1), and receiving autologous stem cell transplant (n=1). While post-discontinuation CD19 data is limited so far, prolonged B-cell depletion up to >1.5 years after last OCR infusion was seen in one patient age >70 years old. Conclusions: In this real-life cohort, >15% of patients treated were above the age of 55 years old, a population which was not included in clinical trials. A quarter of patients >55 years old stopped OCRmost commonly for disease progression, severe infections or presumed unfavorable risk/benefit ratio. Indeed, one death occurred due to pneumonia, as well as an instance of prolonged B-cell depletion after OCR discontinuation. Our data highlight some of the risks in an older cohort on OCR and emphasize the need to study this population to better inform conversations about the risks this treatment.