<h3>Objective:</h3> To ascertain the frequency of Neuromyelitis Optica Spectrum Disease (NMOSD) misdiagnosis as Multiple Sclerosis (MS), and thus related use of FDA-approved disease-modifying therapies (DMTs) for MS, in a national cohort. <h3>Background:</h3> NMOSD is an antibody-mediated inflammatory disease of the central nervous system (CNS) that targets the optic nerves, spinal cord, and certain brain regions. NMOSD patients may be misdiagnosed with the more common condition of MS, given some shared signs and symptoms. Misdiagnosed NMOSD patients may be exposed to certain MS DMTs that could potentially worsen the morbidity associated with NMOSD. <h3>Design/Methods:</h3> Preliminary de-identified aggregate data was obtained utilizing TriNetX, a federated health research network providing access to statistics on electronic medical records that included sixty-one health care organizations (HCOs) within the United States. Patients with the ICD-10 code of NMO (G36.0) were queried within the database from 2008 to 2022. <h3>Results:</h3> Of the 7768 NMO patients were identified from the TriNETX database, 75.0% were female (n=5826), the mean age (SD) was 49.1 (18.1) years, 53.0% were white (n=4,117), 27.0% (n=2097) were black, 3.0% were Asian (n=223), and the remain are unknown 17.0% (n= 1331). In the four Census Regions, we included 1750 patients from the Northeast, 1012 patients from the Midwest, 4048 from the South, and 872 from the West. Of all NMO patients, 44% (n=3,421) were diagnosed with MS at some point during their course, and 853 NMOSD patients received at least one FDA-approved MS therapy. Sensitive analysis will be completed on geographic variance based on the four censuses of misdiagnosis and prescribed FDA-approved MS DMTs. <h3>Conclusions:</h3> Many NMOSD patients were misdiagnosed with MS in this national population, and almost one-quarter of misdiagnosed patients were prescribed an FDA-approved MS DMT. An understanding of the specific characteristics of misdiagnosed NMOSD patients is warranted to better understand the factors increasing the risk of misdiagnosis. <b>Disclosure:</b> Mr. Wong has nothing to disclose. Dr. Noroozi Gilandehi has nothing to disclose. Miss Francis has nothing to disclose. Alen Delic has nothing to disclose. Dr. Germaine has nothing to disclose. Dr. Wright has nothing to disclose. Dr. Galli has nothing to disclose. Dr. Kadish has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. The institution of Dr. Kadish has received research support from Alexion Pharmaceuticals. Dr. Paz Soldan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Paz Soldan has received research support from National Institutes of Health. The institution of Dr. Paz Soldan has received research support from National Multiple Sclerosis Society. The institution of Dr. Paz Soldan has received research support from Western Institute for Biomedical Research. The institution of Dr. Paz Soldan has received research support from Biogen. The institution of Dr. Paz Soldan has received research support from Novartis. The institution of Dr. Paz Soldan has received research support from Clene Nanomedicine. An immediate family member of Ms. Klein has received personal compensation for serving as an employee of Amgen. An immediate family member of Ms. Klein has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Greenlee has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink. Dr. Greenlee has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Sommers Schwartz Law Offices. Dr. Greenlee has received publishing royalties from a publication relating to health care. Dr. Greenlee has received publishing royalties from a publication relating to health care. The institution of Dr. Rose has received research support from National Multiple Sclerosis Society. The institution of Dr. Rose has received research support from Guthy Jackson Charitable Foundation. The institution of Dr. Rose has received research support from NIH . The institution of Dr. Rose has received research support from VA. The institution of Dr. Rose has received research support from Biogen. The institution of Dr. Rose has received research support from Friends of MS. Dr. Rose has received intellectual property interests from a discovery or technology relating to health care. Dr. Smith has nothing to disclose. Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from Western Institute for Veteran Research. The institution of Dr. Clardy has received research support from NIH/NINDS. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel and Lodging with U of Iowa. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Barrow Neurological Institute. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Beaumont Health.