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ABSTRACTBackground: For interferon beta-1a subcutaneously three times weekly (IFN β-1a SC tiw), administration options include manually injected prefilled syringes; a preassembled, single-use autoinjector; and a reusable autoinjector. This study evaluated patient-perceived ease of use of two injection devices.Research design and methods: REDEFINE, a Phase IV, multicenter crossover study, randomized patients with multiple sclerosis and ≥5 weeks’ IFN β-1a 44 μg SC tiw use to 4 weeks using a single-use autoinjector, then 4 weeks using a reusable autoinjector, or vice versa. The primary endpoint was the proportion rating each ‘easy’ or ‘very easy’, with/without regard to previous device experience.Results: Of 97 randomized patients, 29 had most recent experience with manual injection; 23 with single-use autoinjector; and 45 with reusable autoinjector. 68.4% found using the single-use autoinjector very easy or easy, versus 77.9% for the reusable device (difference −9.5%; p = 0.200). 40.0% versus 29.5% found the respective devices very easy (difference 10.5%; p = 0.203).Conclusions: Most patients found both autoinjectors easy or very easy to use. Having two viable options may help accommodate patient preferences. Ease of administration and patient satisfaction relates to adherence; satisfied patients may more likely be adherent.Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02019550).