OBJECTIVES:  To evaluate the economic and clinical impacts of treatment with subcutaneous peginterferon beta-1a (SC PEG-IFN) vs. SC interferon beta-1a (SC IFN beta-1a) for relapsing multiple sclerosis (RMS) in the United States. METHODS:  A cost-consequence model, adopting a national perspective, was developed to compare costs of SC PEG-IFN vs. SC IFN beta-1a. The model evaluates clinical and economic consequences of switching all patients who are currently on SC IFN beta-1a to SC PEG-IFN using costs and baseline clinical characteristics specific to the US. A Markov model over two years with cycle times of three months was computed. Costs of relapse and disability status are from a cost of illness study (Kobelt et al. 2006). The hazard ratios for clinical outcomes of SC PEG-IFN vs. SC IFN beta-1a treatment were estimated using the results from Tolley et al. 2015 and Coyle et al. 2016. The RMS population treated with SC IFN beta-1a is from actual 2016 utilization. RESULTS:  The number of RMS patients treated with SC IFN-1a was 19,717. The use of SC PEG-IFN in place of SC IFN beta-1a reduced the number of relapses by 10,244 and added 2,129 relapse-free years among the cohort. SC PEG-IFN also slowed disease progression (192 additional patients had an Expanded Disability Status Scale < 6.0 compared to SC IFN beta-1a), and reduced drug costs, relapse costs, and disability status costs. The sum of these cost savings for the cohort was $217,982,252 over two years (86.4% due to drug costs, 12.1% to relapse costs, and 14.5% to disability status cost savings). Total savings per patient were $11,056. CONCLUSIONS:  The results of this model suggest that use of SC PEG-IFN compared with SC IFN beta-1a in the treatment of RMS in the US is a cost-saving strategy. Additional research incorporating adherence and side effects are necessary.