Background: Siponimod was approved in the United States (US) in March 2019 for patients with relapsing forms of Multiple Sclerosis (MS). The efficacy and safety of siponimod were demonstrated in Phase III EXPAND trial. Adherence to disease modifying therapy is correlated to improved clinical outcomes. This analysis provides the first real-world account of adherence in patients initiating siponimod since its approval in the US. Objectives: To assess the baseline demographic, clinical characteristics and adherence in patients with MS initiating once-daily, oral siponimod using a longitudinal patient-level claims database. Methods: This retrospective cohort study, using IBM® MarketScan® Research Databases, included patients with MS initiating siponimod from March 2019-Septermber 2020. The index date was defined as first observed claim for siponimod, and the baseline period was 1-year prior to index date. Patient demographics, clinical characteristics and adherence (defined as proportion of days covered [PDC]) were assessed among patients with 6- and 12-month post-index follow up. Results: Overall, 143 and 34 MS patients initiating siponimod with 6-month and 12-month of follow up, respectively, met study eligibility. Among patients with 6-month follow up, 72% of them were females. Mean age was 52.3 (SD±10.3) years and 10% of patients were ?65 years of age. About 89.5% of patients had commercial insurance while 10.5% had Medicare supplemental. Overall, 33.5% were not on any DMT in the baseline period. Major comorbidities included osteoarthritis (55.9%), dyslipidemia (36.4%), hypertension (33.6%), and fatigue & depression (25.9% each). Nearly ?15% patients had other comorbidities like thyroid disease, chronic pain, urinary tract infections, anxiety, sleep disorders, eye symptoms, and sensory problems. Generally, patient demographics were comparable in patients with 12-month follow-up. Mean adherence was 0.84 (SD±0.22) and 0.81 (SD±0.31) among those with 6- and 12-month follow-up, respectively. Conclusions: Real-world claims data suggest favorable adherence (mean PDC ?80%) among early siponimod initiators. Understanding patient profile and adherence in real-world setting may guide treatment decisions in clinical practice.