AbstractObjectiveOur objectives were to (1) obtain the prevalence and demography of people with multiple sclerosis (MS) in a representative Colorado population, and (2) to assess the utilization of disease‐modifying therapy within this prevalent cohort.MethodsThis is a retrospective, observational study of patients that had contact with the University of Colorado Health System from 2012 to 2020. We queried Health Data Compass, a data warehouse, for patient data and applied the MS Prevalence Workgroup Algorithm to generate a prevalent cohort. We calculated prevalence as of 31 December 2020, and stratified by age, sex, race, and ethnicity. Payer information and treatment exposure were obtained from linked claims from the Colorado All Payers Claim Database. Disease‐modifying therapies were classified as highly effective and moderately effective based on the clinical trial, TREAT‐MS (NCT03500328).ResultsFrom a population of 1,382,821 individuals, 8557 people with MS were captured. Age‐adjusted prevalence of MS as of 31 December 2020 was 572.3 per 100,000 with a mean age of 47.36. Prevalence varied between demographic subgroups, with the lowest prevalence in Hispanic men (215.6) and highest in White (824.1) and Black women (820.1). Overall disease‐modifying therapy exposure was 62.4%, with increased highly effective therapy use and a corresponding decrease in moderately effective therapy use on a yearly basis.InterpretationMS is highly prevalent in a representative Colorado cohort. Overall treatment and proportion of highly effective therapy exposure increased significantly during a critical period of MS therapeutic advances, indicating a shift in disease management driven sharply by the availability of on‐label anti‐CD20 therapy.