<h3>Objective:</h3> Identify associations of traumatic brain injury (TBI) history and subsequent diagnosis of multiple sclerosis (MS). <h3>Background:</h3> MS prevalence has increased since 2013 and has been linked to environmental factors (e.g., smoking history, obesity, Epstein-Barr Virus). More limited data suggest a link between MS and multiple concussions and TBI. This study examined the association of TBI and MS in Post-9/11 era veterans. <h3>Design/Methods:</h3> Our retrospective cohort study included Veterans who received Department of Defense (DoD) care in at least three years FY2000–2019. We identified MS using ICD9 (340) or ICD10 codes (G35). We identified TBI exposure using a hierarchical approach prioritizing data from the DoD Trauma Registry, self-reported loss/alteration of consciousness, or post-traumatic amnesia, and then ICD-9/10 diagnosis. TBI was classified as no TBI, mild TBI, moderate/severe TBI, and penetrating TBI. Index dates were the first date of TBI diagnosis or were simulated by drawing from the distribution of true index dates within age brackets for those without TBI. Other covariates included age, sex, race/ethnicity, health behaviors (e.g., smoking, substance use disorders, overdose, obesity) and comorbid health conditions associated with MS (e.g., depression, anxiety, hypertension, hypercholesterolemia, and chronic lung disease). We conducted competing event (Fine-Gray) analyses examining time from TBI/index day to MS diagnosis. <h3>Results:</h3> Of the 2,291,789 Veterans who met inclusion criteria (mean age=33; SD=11) 16.6% had TBI exposure. Time to MS was fastest for women (HR 2.4; 95%CI 2.2–2.6) and veterans with the following clinical characteristics before index date: stroke (HR 2.1; 95%CI 1.8–2.5), other neurological conditions (HR 2.2; 95%CI 1.8–2.6) and TBI severity (penetrating [HR 1.96; 95%CI 1.5–2.6]; moderate/severe [HR 1.5; 95%CI 1.2–1.8]; mild [HR 1.5; 95%CI 1.3–1.6]). <h3>Conclusions:</h3> Our study found that neurological conditions including TBI were the strongest clinical predictors of MS emergence in this younger Veteran cohort, which should be considered in caring for Post-9/11 Veterans with neurological conditions. <b>Disclosure:</b> The institution of Dr. Pugh has received research support from Department of Defense, Epilepsy Research Program. The institution of Dr. Pugh has received research support from VA Health Services Research and Development Service. The institution of Dr. Pugh has received research support from VA Rehabilitation Research and Development Service. The institution of Dr. Pugh has received research support from Congressionally Directed Research Programs. The institution of Dr. Pugh has received research support from Sanofi. Megan Amuan has nothing to disclose. Dr. Ocier has nothing to disclose. Dr. Graham has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Romaguera Law Group. Dr. Graham has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Lewis Brisbois. The institution of Dr. Graham has received research support from Department of Veterans Affairs. Dr. Graham has received personal compensation in the range of $10,000-$49,999 for serving as a Speaker with MER (non-profit CME provider). Dr. Graham has received personal compensation in the range of $500,000-$999,999 for serving as a Employee with Department of Veterans Affairs. An immediate family member of Dr. Graham has received personal compensation in the range of $100,000-$499,999 for serving as a Exployee with Department of Veterans Affairs. Dr. Adamson has nothing to disclose.