PROJECT SUMMARY/ ABSTRACT Injury to the anterior cruciate ligament (ACL) results in a threat to an active lifestyle and exposes the patient to an increased risk of early post-traumatic osteoarthritis (PTOA). ACL reconstruction is typically chosen by individuals to allow a return to their previous activity level and sports activities. The results of primary ACL reconstruction have been good at restoring short-term functional stability, but patients’ long-term outcome remains unknown. The Multicenter Orthopaedic Outcomes Network (MOON) is an established consortium designed to enroll and longitudinally follow a population cohort of ACL reconstructed patients to determine the predictive risk factors of short and long-term outcomes following ACL reconstruction. The overall objective of this prospective multicenter cohort is to determine both the short and long- term outcomes of these patients, to identify potentially modifiable risk factors for worse outcomes and to determine the incidence of symptomatic PTOA in order to establish patient-specific predictive models of clinically important outcomes. Our previous grants have allowed us to enroll over 2,000 patients and obtain 2, 6, and 10-year follow-up on this parent cohort. The objective of this grant is to longitudinally follow up the cohort at 20 years in order to understand the outcome trajectories of these patients, and to determine who is at highest risk for developing PTOA. These will be accomplished by three Specific Aims. Aim 1 will quantify how much pre- and post-operative risk factors can influence knee pain, which is a proxy for symptomatic PTOA. Aim 2 will determine the incidence of and identify dynamic treatment regimens that maximize a patient’s satisfaction with their surgery at 10- and 20-years post-surgery. Lastly, Aim 3 will determine the incidence of and identify dynamic treatment regimens to avoid early PTOA and total knee arthroplasty (the end-stage equivalent of PTOA).