Among the available disease modifying drugs used in the treatment of multiple sclerosis, there is an increasing relevance of high-efficacy therapies recommended for early use to control the disease activity effectively. In the course of treatment, efficacy as well as safety measures of high-efficacy therapies have to be regularly evaluated. Ocrelizumab, an anti-CD20+ antibody, is the only high-efficacy therapy approved for the treatment of both relapsing-remitting and primary progressive type of multiple sclerosis. Consequently, the drug can be used in a wide population of multiple sclerosis patients. Recently, the cumulative data have been acquired from 10-year follow-up of ocrelizumab use in clinical trials and real-world evidence in as many as 300,000 patients with multiple sclerosis. Based on these data, the general safety profile of the drug has been reviewed (considering the risk of major adverse events, including infusion-related reactions, infections and malignancies), along with specific aspects associated with vaccines and pregnancy/post-partum period. Moreover, the indices of adherence and persistence in long-term treatment with ocrelizumab have been analysed, together with their potential contributing factors. The above data indicate that treatment with ocrelizumab has a beneficial safety profile and is well-tolerated by patients with multiple sclerosis, which supports the choice of ocrelizumab as a therapeutic option. Ongoing clinical and observational trials and registries will provide further data on the safety of the drug, which would allow an update of recommendation in this field.