OBJECTIVES: Multiple sclerosis (MS) is an inflammatory, neurodegenerative condition of central nervous system with prevalence of 1 Million worldwide (age at first manifestation 20-40 years). MS may lead to permanent disability and early retirement even in young adults. The purpose of this analysis was to provide an economic assessment of relapsing-remitting MS-treatment with Natalizumab versus Interferons and Copolymer in 4 European countries (Austria, Czech Republic, Slovakia, Slovenia). METHODS: The analysis was performed using a Markov model. The model allows a treatment switch due to relapse. Efficacy assessment was based on the outcome measure “relapse-free patients”. Costs were captured for the year 2010. Resource use was determined from results of a survey conducted by the Austrian MS Society and accurately reflects the therapeutic approach. Resource use of Czech Republic, Slovakia and Slovenia was determined via country-specific research. Where country specific data could not be captured, Austrian data was adjusted via Purchasing Power Parities (PPP). The study time horizon was 2 years.  The analysis was performed from the perspective of the health care system of the 4 European countries. RESULTS: In Czech Republic the average cost of the therapy algorithm Natalizumab amount to €33,835 per patient within the time horizon of 2 years versus €22,896 (Interferon) and €21,256 (Copolymer). A patient successfully treated with Natalizumab accounts for €56,525 compared to €70,190 (Interferon) and for €87,555 (Copolymer). In Slovakia a relapse-free patient values €60,357 (Natalizumab) versus €58,043 (Interferon) and €19,921 (Copolymer). A relapse-free patient in Slovenia values €59,108 (Natalizumab) versus €66,202 (Interferon) and €84,207 (Copolymer). In Austria a relapse-free patient values €58,423 (Natalizumab) versus €71,906 (Interferon) and €89,591 (Copolymer). CONCLUSIONS: In Czech Republic, Slovenia, and Austria, treatment of MS with Natalizumab is more cost-effective than Interferon resp. Copolymer 1 therapy. Switching to effective and more expensive alternatives does not account for higher health care costs.