Background: Ocrelizumab (OCR) is a humanized, monoclonal antibody targeting CD20+ B cells and is approved for treatment of relapsing remitting (RRMS) and primary progressive MS (PPMS). The ACAPELLA trial is a prospective study with a primary objective of assessing OCR-associated adverse events (AEs) in a real-world MS population. ACAPELLA includes patients with preexisting conditions exempted from the phase II & III clinical trials, such as a prior history of malignancy, prior immunosuppressive treatment, and more advanced age and/or disability. Objectives: We sought to describe the occurrence of serious infections and malignancies in a real-world population receiving OCR, including those with characteristics outside the inclusion parameters of the phase II and III trials. Methods: The study includes all subjects treated with OCR at the Elliot Lewis Center since its commercial release in March 2017. Initial assessments include EDSS, brain MRI, mammograms (standard of care), collection of medical history including prior serious or recurrent infections, history of malignancy and exposure to immunosuppressive treatment, JCV index, and CD19 count. Results: As of January 2021, 332 subjects were enrolled, 228 subjects had reached 12 months of treatment, 166 subjects had reached 18 months, 148 subjects had reached 24 months, and 90 subjects had reached 30 months. Subjects were 29% male, 71% female, with an age range of 18-73. Sixty two percent had RRMS and 38% PMS (PPMS and SPMS) with an EDSS range of 07.5; 24% had a baseline EDSS of ? 6.0 with a median of 3.0. Three percent of subjects had a serious infection (defined as requiring hospitalization). Four percent of subjects had clinical or MRI relapses; 9% of subjects had a history of prior neoplasm (excluding basal cell carcinoma). Three new malignancies occurred during OCR treatment. Conclusions: Thus far, the incidence of AEs is comparable to that seen in the phase III trials and in previously reported ACAPELLA data. Additional topics of interest in the ACAPELLA population include the effect of continued OCR dosing on JCV index values and immunoglobulin levels, and changes in EDSS and MRI over time.