Studies have shown that natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). To date, no data are available in Portuguese patients.To determine the efficacy and safety of natalizumab in patients with RRMS in routine clinical practice in Portugal.Clinical data for adult patients with RRMS treated with natalizumab at specialist neurology centres in Portugal were entered retrospectively into a database for analysis between October 2010 and February 2012. Changes in annualized relapse rates (ARR), Expanded Disability Status Scale (EDSS) scores and disability status were analysed.A total of 383 patients from 20 centres were included. Prior to starting natalizumab, the baseline median EDSS score was 4 and the mean ARR was 1.64. Most patients had previously received multiple sclerosis treatment (93.0%). Median natalizumab treatment duration was 12 months. Natalizumab treatment was associated with significant (p = 12 months (n = 288) and for >= 24 months (n = 160). Natalizumab was more effective in patients with less disability (EDSS < 3) and in those who had not previously received disease-modifying treatments. Two cases of progressive multifocal leukoencephalopathy were reported. No new unexpected adverse events occurred.Natalizumab is well tolerated, and is effective in reducing relapse rate and stabilising disease in patients with RRMS in the clinical practice setting in Portugal. Its efficacy persists with continued treatment, and it may be particularly effective in patients with less disability and without prior disease modifying therapy.