Ocrelizumab demonstrates positive outcomes in patients with multiple sclerosis. However, approximately 40% of patients experience infusionrelated reactions (IRRs), which can reduce adherence despite premedications. This review examines the safety of shortened infusion protocols in reducing IRRs and improving the patient experience. Additionally, other strategies for minimizing IRRs are discussed. Scopus, PubMed, and the Cochrane Library were searched up to November 30, 2024, for cohort studies, as well as randomized and non-randomized clinical trials. Seven studies were included following two stages of screening. The primary outcome was a documented reduction in the incidence rate of IRRs. The seven included studies comprised a total of 1,834 patients. Overall, shorter-infusion protocols were found to be safe as conventional protocols, with only a slight increase in IRR incidence. Patients receiving shorter infusions at home reported higher satisfaction, comfort, and confidence. Splitting the first dose appears to be safer than administering a full dose at once, although a single full dose is also relatively safe. Shorter infusion rates and a single full dose of ocrelizumab are generally preferred to save time and effort. Premedication has been shown to reduce IRRs, and patients report greater comfort with at-home infusions. Further clinical trials are needed to evaluate all proposed procedures and to establish a comprehensive understanding of the optimal management strategies for ocrelizumab-related IRRs.