<h3>Objective:</h3> To explore the clinical presentation of MS and neuromyelitis optica spectrum disorder (NMOSD) in patients of Asian ancestry in the United States. <h3>Background:</h3> Race and ancestry influence the course of demyelinating conditions like Multiple Sclerosis (MS). Asian patients are underrepresented in clinical research in the United States. <h3>Design/Methods:</h3> Demographic, clinical and radiologic data were extracted from the medical record for adults with Asian self-identified race and diagnosis of demyelinating disease cared for at a single North American MS center between 2006/02/06 and 2022/06/09. Descriptive statistics were used to describe the cohort, then demographic and clinical factors were compared according to region of ancestry. <h3>Results:</h3> The cohort included 282 patients from 11 different countries; 73.1% were born in Asia. Most patients (94.7%) preferred English for medical communication, but fewer of East Asian ancestry did (p=0.0001). South Asian ancestry was associated with higher neighborhood household income (p=0.002) and Southeast Asian ancestry with smoking (p=0.08). Diagnoses included MS (76.2%) and NMOSD (13.8%). More patients with NMOSD than MS were of East Asian and Southeast Asian ancestry (p=0.004). For MS patients, levels of optic nerve and spinal cord involvement were similar across regions of ancestry. Most (83.7%) patients were currently on MS treatment (42.3% on antiCD20 therapies). MS Severity Scale (MSSS), while similar to the clinic average. was worse with Southeast Asian ancestry (p=0.006) and also worse with smoking, and lower neighborhood median household income or educational attainment. <h3>Conclusions:</h3> Patients of Asian ancestry are underrepresented in research in the United States. In this cohort, Asian patients with MS were actively treated and disease severity reflected the overall clinic. Both region of origin and neighborhood socioeconomic factors were associated with disease characteristics. Further research is needed to uncover genetic, socioeconomic, or environmental factors accounting for worse MSSS in Southeast Asian patients. <b>Disclosure:</b> Dr. Fan has nothing to disclose. Ms. Alexander has nothing to disclose. Mr. Poole has nothing to disclose. Ms. Wijangco has received research support from National Institutes of Health. Dr. Henson has received personal compensation for serving as an employee of Piedmont Healthcare. An immediate family member of Dr. Henson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Tempus. Dr. Henson has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for various law firms. Ruth Dobson has nothing to disclose. Dr. Guo has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Roche Genentech. The institution of Dr. Bove has received research support from Novartis.