OBJECTIVES  Quasi-experimental analysis to determine the effect of an opt-in telephone intervention on adherence in patients using subcutaneous interferon β-1a, which is indicated for relapsing-remitting multiple sclerosis. Drop-out reasons, side-effects, and expectations of therapy are described. METHODS  Customers of a mail-order pharmacy that services Germany who ordered subcutaneous interferon β-1a were targeted for enrollment in a free program that included an initial counseling call, optional e-mail reminders for the next doctor’s consultation and prescription, and ongoing counseling calls. Patients enrolled in the program for at least 6-months were included in the analysis and compared to patients that did not enter the program over the same time period. Proportion of days covered (PDC) was calculated for each group and compared using analysis of variance. Enrollees in the program were administered a questionnaire at the initial welcome call addressing their expectations of therapy, and again during each counseling call regarding their compliance behavior, and side effects. RESULTS  Patients in the adherence program showed an unadjusted PDC 8.2% higher than the control, F(1.247)=13.44, p=0.0003. One program patient switched drugs compared to six control group patients. A total of 21% of enrolled subjects reported missing at least one dose. Side-effects included pain/inflammation at the site of injection (24.41%), fatigue (20.73%), headaches (17.06%), and flu-like symptoms (9.71%). Exacerbations were reported by 15.7% of patients. Patients’ had expectations that therapy would prolong the distance between exacerbations (23.36%) and slow the progression of disability due to the disease (21.28%). CONCLUSIONS  Actively recruiting patients into an optional adherence program significantly increased the compliance rate for relapsing-remitting multiple sclerosis patients using subcutaneous interferon β-1a. Side effects experienced by enrolled patients were consistent with the package insert. Limitations include a potential bias between patients that agree to the program vs. those that do not, as well as the lack of additional questionnaire data from the control group.