The purpose of this prospective study was to investigate whether self-efficacy, hope, level of disability, perceived support, and previous use of an immunomodulatory therapy when measured at the initiation of a therapy can accurately predict adherence. A convenience sample included 108 individuals with multiple sclerosis who initiated therapy with glatiramer acetate (Copaxone), plus or minus 21 days, and completed instruments online that included the Multiple Sclerosis Self-Efficacy Scale (MSSE), the Herth Hope Index, Performance Scales, and a sociodemographic data sheet that included questions about previous use of immunomodulators and individuals considered most supportive of glatiramer acetate therapy. Logistic regression analysis revealed that the MSSE total (Control and Function subscales combined) was the only significant predictor of adherence. The higher the score, the more likely the individual was to adhere to glatiramer acetate. Those in the adherent group had a significantly greater level of self-efficacy. The MSSE measured at the initiation of glatiramer acetate therapy correctly classified 98.8% of those who were adherent at the 6-month follow-up. For each unit of increase in score, the likelihood of adherence increased. This prospective study revealed that the MSSE, when measured at the initiation of therapy, seems useful in predicting adherence category at the 6-month follow-up.