Background: More than 3,000 multiple sclerosis (MS) patients were treated with disease-modifying drugs (DMDs) in the Region of Valencia during 2005-2014. We aimed at describing the demographic and clinical characteristics of MS patients who requested treatment with DMDs, variations in their use, and the factors associated with change to second-line therapies during this decade. Methods: A retrospective cohort study with information from Subcomité Especializado de Medicamentos de Alto Impacto Sanitario y/o Económico registers. A statistical analysis was run in 2 phases: descriptive analysis of the sample using classical statistical methods, and of DMD trend by a chi-square test for linear trends; analytic analysis to examine the factors associated with change to second-line treatment (logistic regression model). Results: We selected 2,205 patients (mean age 32.12, SD 9.64; 70% females, and 86.6% remising-remitting MS (RRMS)); 1,012 patients were attended to in highly specialized MS units (45.8%); 525 in monographic units (23.8%); and 668 in general units (30.2%). DMD prescriptions increased, and glatiramer acetate was more widespread at the end of the period (35.4%). Conclusion: Variability in access to different treatments was slight. The younger the patient, the higher the risk of first-line RRMS treatment failing in female gender and first treatment with interferon.