PROJECT SUMMARY/ ABSTRACT Revision anterior cruciate ligament (ACL) reconstruction represents an infrequent but clinically important challenge in orthopaedic practice. It is commonly reported that the results of revision surgery remain inferior to primary ACL reconstructions, while the etiology of these poorer outcomes compared with primary reconstructions remains unknown. With this in mind, the Multicenter ACL Revision Study (MARS) group was established as an 83-surgeon multicenter consortium to perform a prospective longitudinal cohort analysis of revision ACL reconstruction outcomes. This is a mixed group of academic and private practice physicians and has been supported and endorsed by the American Orthopedic Society for Sports Medicine (AOSSM). Over 1,200 patients were enrolled and have now been followed beyond ten years. Our previous grant built on previous 2 and 6-year follow-up and obtained 10-year follow-up on the entire cohort (patient-reported outcome measures and incidence of subsequent surgeries), as well as collecting 10- year onsite follow-up within a nested cohort for radiographic and clinical measures. Radiographic onsite follow-up demonstrated structural post-traumatic osteoarthritis (PTOA; Kellgren-Lawrence grades 3-4) in 56% of the onsite cohort. Previous meniscectomy proved to be a predictor for this severe structural OA, but 60% did not have a previous medial or lateral meniscectomy. Thus, this proposed grant will utilize genomics targeted for OA predictors to seek to determine a more comprehensive risk profile for patients for symptomatic and structural PTOA. Predictors of risk will guide revision surgical decisions and post-surgical activity and lifestyle guidance, as the spectrum of resulting PTOA may be influenced by genetic variation. Additionally, predictors and outcomes for total knee arthroplasty in these young active patients will be assessed. Validated patient-reported outcome measures will assess outcome at 20 years with analysis for predictors to continue to build upon 2, 6 and 10-year follow-up in order to shape the care of these challenging patients.