OBJECTIVES: Evaluate patient outcomes for a new formulation of the multiple sclerosis (MS) drug glatiramer acetate (GA) associated with reduced injection-related pain.  METHODS: This retrospective, closed-cohort study included adults from the Truven MarketScan Commercial database with: ≥2 claims with MS diagnoses, ≥6 months of continuous GA treatment before approval of the new formulation, and ≥6 months of data after the index date (earliest claim for new formulation [switchers] or GA claim closest to index date of match [non-switchers]). Non-switchers were propensity-score matched 1:1 to switchers using baseline demographics, comorbidities, resource use, and costs. Adherence (measured by proportion of days covered) and direct costs were compared for switchers and non-switchers 6 months following the index date. Difference-in-differences analysis compared outcomes 6 months before and after the index date. Wilcoxon signed-rank and McNemar’s tests for matched pairs compared continuous and categorical measures, respectively. Outcomes were also assessed using multivariate regression analyses.  RESULTS: Within 6 months of approval, approximately 42% of patients switched to the new GA formulation (switchers, n=1,362; non-switchers, n=2,093). After matching, there were no significant differences in demographics, comorbidities, or baseline costs. Following approval of the new formulation, switchers had significantly better adherence than non-switchers (90% vs 80%; p<0.0001) and total costs for switchers were $221 less than non-switchers (p=0.01), driven by reduced medical costs of $1,882 (p=0.17). Difference-in-differences analysis demonstrated improved adherence (+2 vs -8 percentage points; p<0.0001) and $508 lower increase in total costs relative to baseline for switchers versus non-switchers (p=0.005). In multivariate analyses, switchers were predicted to have a 13% increase in adherence (90% vs 80%; p<0.0001) and 22% reduction in medical costs ($8,798 vs $11,255; p=0.002).  CONCLUSIONS: The new formulation of GA with reduced injection-related pain improved adherence and reduced medical costs. Reformulation of other therapies that reduce injection-related pain may provide similar benefits.