Since the beginning of the mass immunization of patients with multiple sclerosis (MS), many data on the efficacy and safety of COVID-19 vaccines have been produced. Considering that MS is an autoimmune disease and that some disease-modifying therapies (DMTs) could decrease the antibody response against COVID-19 vaccines, we carried out this retrospective study with the aim to evaluate the safety of these vaccines in terms of AEFI occurrence and the antibody response after MS patients had received the third dose. Two hundred and ten patients (64.8% female; mean age: 46 years) received the third dose of the mRNA-based COVID-19 vaccine and were included in the study. Third doses were administered from October 2021 to January 2022. The majority of patients (n= 193) were diagnosed with RRMS and EDSS values were ≤3.0 in 72.4% of them. DMTs most commonly used by included patients were interferon Beta 1-a, dimethyl fumarate, natalizumab and fingolimod. Overall, 160 patients (68.8% female) experienced 294 AEFIs, of which about 90% were classified as short-term, while 9.2% were classified as long-term. The most commonly reported following the booster dose were pain at the injection site, flu-like symptoms, headache, fever and fatigue. Regarding the immune response, consistently with literature data, we found that patients receiving ocrelizumab and fingolimod had lower IgG titer than patients receiving other DMTs.