OBJECTIVES: To evaluate the clinical and economic benefits of treatment with peginterferon beta-1a (PEG-IFN) vs. glatiramer acetate (GA) for relapsing-remitting multiple sclerosis (RRMS) patients in Spain. METHODS: A Markov model compared the outcomes of treating patients with PEG-IFN vs. GA from a societal perspective in Spain. The model estimates clinical and economic consequences of initiating treatment with PEG-IFN among all patients who would receive GA based on current GA market share (including GA 20 mg/mL and 40 mg/mL). Costs, resource utilization, and baseline Expanded Disability Status Scale (EDSS) distribution were specific to Spain. Costs of relapse and disability status were from a cross-sectional cost of illness study. Hazard and risk ratios for clinical outcomes of PEG-IFN vs. GA 20 mg/mL were estimated from an indirect treatment comparison. The model incorporates a 10-year time horizon with three-month cycles. RESULTS: The number of RRMS patients treated with GA was 4,880. Within the model, across 10 years, the use of PEG-IFN in place of GA would reduce the number of relapses by 6,824 and relapse costs by €22.2 million. PEG-IFN was shown to slow disability worsening, with 14.1% fewer patients progressing to EDSS ≥ 6.0 and 10.0% more patients remaining at EDSS ≤ 3. Costs associated with disability would be reduced from €938.1 million to €841.1 million, driven by reduced informal care (€47.8 million savings) and community services costs (€16.0 million savings). Total direct cost savings for the cohort would approach €34.3 million (€7,027 per patient). Total indirect cost savings would exceed €160.0 million (€32,795 per patient). CONCLUSIONS: The results of this model suggest that use of PEG-IFN compared with GA in the treatment of RRMS in Spain is a potential cost-saving strategy that could moderate healthcare resource use and improve patient outcomes. Additional research using real-world comparative effectiveness studies should be conducted