Background: Natalizumab is a humanized monoclonal antibody with high efficacy and an acceptable safety profile used in the treatment of patients with multiple sclerosis (MS). Objectives: Our aim was to report data regarding long-term administration of Natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) from our clinic. Methods: A retrospective observational study was performed including RRMS patients who underwent treatment with ≥ 24 Natalizumab infusions. We analyzed the EDSS values, the relapse rate and the rate and type of adverse events related to Natalizumab administration. Results: 51 subjects were included with a predominance of women (62.74%), an average age of 40.43±1.49 years, a mean disease duration of 9.86±0.7 years and mean number of Natalizumab infusions of 45.58±2.74. An increased number of patients (80.39%) were relapse-free and there was observed a mild reduction of the mean EDSS value following Natalizumab initiation in patients who had not been treated with other disease modifying therapies anteriorly. Among the encountered adverse events we registered: increased liver transaminases (13.72%), local infections (7.84%) and dysmenorrhea in one patient. The rate of severe adverse events was 3.92 and there were registered no cases of Progressive Multifocal Leukoencephalopathy (PML). Conclusions: Natalizumab proves to be effective, has an adequate safety profile and can be administered with good tolerability for a rather extended period of time, provided that the patients are closely monitored.