OBJECTIVES: Teriflunomide 14 mg is the only first-line DMT with significant reduction in both relapses and 12-week disability progression in 2 pivotal clinical trials. Cost-effectiveness of teriflunomide 14 mg once daily orally vs other first-line DMTs for RRMS (oral dimethyl fumarate [DMF] 240 mg twice daily; subcutaneous glatiramer acetate (GA) 20 mg daily, interferon ([IFN] β-1a 44 µg 3×/week, and IFNβ-1b 250 µg every other day; intramuscular IFNβ-1a 30 µg once weekly) and best supportive care (BSC) were evaluated in the Finnish healthcare payer setting. METHODS: The primary outcome was incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained vs nondominated alternatives). Markov cohort modeling with a 20-year time horizon (3%/year discount rate) was employed. During each 1-year modeling cycle, patients could maintain their Expanded Disability Status Scale (EDSS) score or experience progression, develop secondary-progressive MS (SPMS), have EDSS progression in SPMS, or experience relapse with/without hospitalization or death. Patient characteristics, standardized mortality ratios, and an RRMS progression matrix were derived from a Finnish MS registry. Specific annual adverse event (AE) risks were included. A mixed-treatment comparison informed treatment effects. EQ-5D quality-of-life estimates and Finnish direct costs were associated with EDSS scores, relapses, and AEs. Robustness of base case results was tested with probabilistic sensitivity analyses (PSAs). RESULTS: Teriflunomide was less costly with higher QALYs vs GA and IFNs. DMF brought marginally more QALYs than teriflunomide (0.129 over 20 years); this difference was associated with higher costs. The ICER for DMF vs teriflunomide was 78,092, and teriflunomide had the lowest ICER of 17,326 vs BSC. In the PSAs, teriflunomide had over 50% cost-effectiveness probabilities, with willingness-to-pay values below €94,000/QALY gained vs other first-line DMTs. CONCLUSIONS: The cost-effectiveness of teriflunomide 14 mg once daily vs DMF twice daily and dominance over other first-line DMTs for RRMS were demonstrated in this Finnish study.