OBJECTIVES: To assess the costs of oral treatment with fingolimod (Gilenya®) compared to intravenous infusion of natalizumab (Tysabri®) in patients with relapse remitting multiple sclerosis (RRMS) in the Netherlands.  METHODS: A cost-minimization analysis (CMA) was used to compare the costs of both treatments. In this analysis drug acquisition costs, drug administration costs, and other costs related to drug treatment were distinguished. Costs were discounted at 4%, and incremental model results were presented over a 1, 2, and 10 year time horizon. The robustness of the model results was determined by means of a number of deterministic univariate sensitivity analyses and a probabilistic sensitivity analysis. Additionally, a break-even analysis was carried out to determine at what IV infusion costs a cost neutral outcome would be obtained.  RESULTS: When fingolimod was compared to natalizumab, the model predicted discounted incremental costs of -€1,699 (95%CI: -€2,216;-€946), -€4,094 (95%CI: -€5,017;-€2,625), and -€20,218 (95%CI: -€24,192;-€13,977) over a 1, 2, and 10-year time horizon respectively. Results of the sensitivity analyses showed that these predictions were most sensitive to changes in the costs for IV administration of natalizumab. Changing these costs within a range of €217 and €297 per IV infusion, resulted in cost savings varying from €15,831 to €24,606 after 10 years. The additional break-even analysis showed that IV infusion costs needed to be as low as €127 and €73 in order to obtain a cost neutral result after 1 and 10 years respectively.  CONCLUSIONS: The present analysis showed that treatment with fingolimod resulted in considerable cost savings compared to natalizumab: €20,218 per RRMS patient in the Netherlands after 10 years of treatment. The robustness of this estimate was confirmed within the sensitivity analyses. The conclusions were in line with cost-utility analysis that has been performed as well, showing cost savings of fingolimod compared to natalizumab.