This study assessed patient perceptions of using a smaller needle (1-inch, 25-gauge) to administer weekly intramuscular (IM) interferon beta-1a (IFN -1a [Avonex]) injections. Patients received 1 IM IFN -1a injection at baseline using the standard needle (1.25-inch, 23-gauge), followed by 4 weekly injections using the smaller needle. The primary end points were change in self-reported visual analog scale scores for preinjection anxiety and postinjection pain, assessed at baseline and once weekly during the 4 weeks of therapy with the smaller needle. Secondary evaluations included assessment of patient perception of ease of use and fear of self-injection with 2 questionnaires, and changes in the number of injection-site reactions. Patients had a mean decrease of 25 ± 31 mm (baseline mean, 46 mm; 4-week mean, 21 mm; p = .0002) in anxiety score and a mean decrease of 22 ± 29 mm (baseline mean, 41 mm; 4-week mean, 19 mm; p = .0003) in pain score. Overall, patients thought the smaller needle was easier to use than the standard needle. Qualitative measurements suggested patients who self-injected IM IFN -1a experienced less fear when using the smaller needle. Preinjection preparation parameters decreased throughout the course of the treatment period. No patients experienced injection-site reactions with the smaller needle. Patients preferred using a smaller needle to administer their weekly IM IFN -1a injection.