OBJECTIVES:  To analyze alemtuzumab IV 12mg budget impact (BI), in patients with relapsing forms of multiple sclerosis (MS), in comparison with fingolimod and natalizumab, in the Spanish National Health System (SNS). METHODS: BI was performed from the SNS perspective. A time horizon of 5 years was chosen (2015-2019) and two scenarios were compared; introduction of alemtuzumab vs. standard treatment (fingolimod and natalizumab) with an initial fixed cohort of 100 patients. Direct healthcare costs considered were treatment (drugs and administration), monitoring, management of potential adverse events (AEs) and disease management. The distribution of patients was stablished according to 2015 Spanish market shares. Patients receiving additional courses of alemtuzumab were estimated with 5 years data of pivotal trials follow-up. Annual treatment costs were calculated with public prices and compulsory deductions. To estimate resources consumption in administration and monitoring, SmPC and risk management plans data were used. For AEs’ management, SmPC data and experts opinion were used. Sensitivity analysis was performed for variations in percentage of patients requiring alemtuzumab’s additional courses and price scenarios. RESULTS:  Base case results estimated total savings of 3.7million€ in 5Y for treating 100 patients with alemtuzumab instead of natalizumab and fingolimod. The most relevant variable contributing to savings was treatment cost of alemtuzumab, due to durability of effect in the absence of continuous dosing dose. Alemtuzumab’s annual treatment cost/patient was 34.687.5€ the 1^rst course, 20.812.5€ the 2^nd and following courses and the average annual treatment cost/patient was 12.515€. Mean savings per patient reached 512€ in 5Y. Disease management costs were lower in the alemtuzumab scenario due to lower relative rate of annual relapses. CONCLUSIONS: The introduction of alemtuzumab in the Spanish SNS brings significant improvements in the budget impact, with total savings of 3.7M€ over five years. All scenarios performed in the sensitivity analysis were consistent with the base case.