OBJECTIVES: Relapsing-remitting multiple sclerosis (RRMS) is the most common form of MS and is characterised by inflammatory episodes in the brain followed by periods of remission. Damage caused by relapses accumulates over time and many patients will develop some form of permanent disability after 10 years. Natalizumab 300mg, fingolimod 0.5mg and INFβ-1a 44mcg are typically considered for treatment-experienced patients with RRMS. This meta-analysis aimed to assess the efficacy of natalizumab versus other potential treatments for RRMS. METHODS: Electronic searches of Medline, Embase and the Cochrane library were undertaken to identify potential studies conducted in adults with RRMS treated with natalizumab, fingolimod or INFβ-1a. Direct meta-analysis was conducted in STATA version 12 using the metan package. Indirect comparisons between treatments via common comparators were made using the Bucher method. RESULTS: Out of 2512 records obtained from systematic searches, forty studies were included in the final data set. Analysis of evidence suggested that patients treated with natalizumab were twice as likely to remain free from disease activity (ie free from both clinical and radiological activity) at 24 months compared with fingolimod (OR=2.05, 95% CI: 1.127, 3.735). Progression of disability (i.e. increase in EDSS score) was lower in patients treated with natalizumab compared with fingolimod (mean difference in EDSS score change= -0.69, 95% CI: -0.882,-0.498). Patients treated with natalizumab had a 50% lower chance of relapse per year compared with INFβ-1a (OR=0.5, 95% CI: 0.391, 0.640). Likewise, patients receiving fingolimod were less likely to have a relapse in a year compared with INFβ-1a (OR=0.64, 95% CI: 0.477, 0.867). Analysis of additional outcomes based on limited data, showed directional favour towards natalizumab compared with fingolimod and INFb-1a without reaching statistical significance. CONCLUSIONS: Compared with fingolimod and IFNb-1a, natalizumab was shown to be a more effective treatment alternative for RRMS patients in this analysis.