We systematically reviewed adverse events (AEs) for ocrelizumab for multiple sclerosis (MS). We searched Medline, Embase, Web of Science, and Toxicology Data Network-TOXLINE (inception to 8-July-2020), clinical trial registries, and product monographs for any clinical trials, observational studies or case reports examining AEs to ocrelizumab. Studies with/without a comparator drug or placebo were eligible. Seventy-eight records were included (4 randomized controlled trials (RCTs), 4 open-label trials, 29 observational studies, and 27 case reports). AEs affected 2756/4498 (61.3%) of ocrelizumab-exposed patients. The most common AEs were infections (n=1342, 39.2% of ocrelizumab-exposed patients) and infusion-related reactions (n=1391, 26.2%). Compared to beta-interferon, infections were more likely in ocrelizumab-exposed patients (Risk Ratio (RR)=1.10; 95% confidence interval (CI):1.01–1.19), including: herpes-related (RR=1.75; 95%CI:1.11–2.76), respiratory tract-related (RR=1.42; 95%CI:1.10–1.84 and RR=1.61; 95%CI:1.10–2.35), nasopharyngitis (RR=1.47; 95%CI:1.13–1.90), and rhinitis (RR=4.00; 95%CI:1.13–14.14). Infusion-related reactions (RR range: 1.57–4.42) were more common for ocrelizumab versus placebo or beta-interferon. From pooled analyses (three RCTs), the risk of ‘any’ serious AE did not differ significantly between the ocrelizumab and comparator groups. However, insufficient data were available to assess longer-term AEs, e.g., malignancy.