Background: In patients with multiple sclerosis (MS), adherence and persistence to disease-modifying therapies (DMTs) are important to maintain treatment efficacy. Factors such as dosing schedule and adverse events (AEs) may impact adherence and persistence. Objectives: Compare adherence and persistence levels with peginterferon beta-1a (PEG) and other injectable DMTs in MS patients. Methods: This study utilized MarketScan data from May 1, 2014 to September 30, 2019 in MS patients in commercial plans who initiated an injectable DMT and had ?12 months of follow-up. Data from patients treated with subcutaneous (SC) PEG once every 2 weeks (n=275), intramuscular interferon (IFN) beta-1a once per week (QW; n=314), SC IFN beta-1a 3 times per week (TIW; n=463), SC IFN beta-1b every other day (QAD; n=236), SC glatiramer acetate (GA) once daily (QD; n=361), and SC GA TIW (n=2198) were included. Adherence (proportion of days covered [PDC] ?80%) was assessed by DMT schedule and index year using a logistic regression model. Persistence (time to discontinuation/switch) was assessed using a Cox regression model. Models were adjusted for age, gender, Charlson comorbidity index, comorbidities, MS-related symptoms, and MS severity score. Results: The overall proportion of adherent patients was numerically lower for PEG (40.7%) than for IFN beta-1a QW (46.2%), IFN beta-1a TIW (43.2%), IFN beta-1b QAD (44.1%), or GA TIW (50.5%), but not GA QD (24.7%). GA QD patients had significantly lower odds of being adherent (odds ratio [OR], 0.44; P<0.0001), whereas GA TIW patients had significantly higher odds of adherence (OR, 1.50; P=0.0021) compared to PEG patients. All other adherence comparisons were not statistically significant. The average PDC for PEG patients increased from 48.9% in 2014 to 73.8% in 2018 and was highest among all examined DMTs in 2018. Compared with PEG patients, GA QD patients were more likely to discontinue/switch (hazard ratio [HR], 1.68; P<0.0001), whereas IFN beta-1a QW (HR, 0.74; P=0.0276) and GA TIW (HR, 0.60; P<0.0001) patients were less likely to discontinue/switch. Conclusions: Persistence and adherence were higher for PEG than for GA QD but not for GA TIW. This finding cannot be explained solely by the dosing schedule and may relate to the higher incidence of flu-like symptoms with IFNs than with GA. These results highlight an increase in PEG adherence that may reflect the increase in education and training on setting expectations for potential AEs.