Posttraumatic Osteoarthritis (PTOA) often results from knee ligament injuries such as to the anterior cruciate ligament (ACL). Patients with ACL injuries are a unique population the initiation event for the development of PTOA is often known. Enrolment of these patients and the prospective collection of “early” information on this population is challenging as the majority in the USwill not be seen by a specialist until severalweeks after injury. We here describe the early lessons learned from the “Multicenter Orthopaedic Outcome Network Early-Anti-inflammatory Treatment in Patients with Acute ACL Tear and Painful Effusions” (MOON-AAA) clinical trial. This is the first US-based multicenter, randomized, good clinical practices (GCP) interventional clinical trial recording biomarker profiles, standardized X-rays as well as patient reported outcomes (PRO’s) in isolated ACL tears seen within 4 days after ACL injury. Methods: This is a GCP multicenter clinical trial enrolling patients with primary isolated ACL tears within 4 days after injury. Inclusion criteria follow the MOON -protocol (Table 1). All patients undergo aspiration of the post-injury effusion within 4 days and 10 days post-injury. Patients receive an injection with 40 mg Kenalog within 4 days, 10 days, both time points or not at all (saline injection control). Permutated block randomization into one of these four groups is done at the time point of the first aspiration. Blinding of patients and investigators is maintained throughout the study. Serum, synovial fluid and urine collection is performed at the first and second aspiration as well as at the time of ACL reconstruction. Synaflexor standardized flexion weightbearing X-rays are obtained on patients pre-operatively. Patient reported outcomes are being collected at 6 time points up to 6months post-ACL reconstruction with a focus on function and symptoms (IKDC, KOOS) activity level (Marx-score), quality of life (KOOS-QOL, SF36) and pain (VAS, KOOSpain, Catastrophizing scale, CSQ). Results: Only data from one cohort are available to date. Our practice performs w 400 ACL reconstructions annually. Pre-study data showed capture of 85.7% of all ACL injuries occurring in Fayette County: 66% of patients were seen within 30 days after ACL injury; 37% were seen by a Surgeon but 73% were seen by a Surgeon or PCP within 1 week of injury; 30% were seenwithin 4 days of injury. A total of 10 patients were eligible for enrollment in a 4 month time period. After this pre-study data changes were made to the study design including development of an “early warning system” through physician extenders in high schools and placement of additional physician extenders in the clinics to help with enrollment. These changes allowed for enrollment of 30 patients in a 7 month time period, a 220% increase in enrollment numbers from the prestudy period. 10–20% of all patients with ACL tears fulfill the inclusion criteria. Screen failures occur at a rate of 25–30% due to either accompanying injuries (n 1⁄4 6) or patient refusal (n 1⁄4 4). No patient withdrew from the study. One patient refused the second knee joint aspiration. No patient was lost to follow-up. No problems were encountered regarding the data collection, specimen storage or patient follow-up. Conclusions: ACL patients can be recruited to a PTOA prevention trial within 4 (þ 4) days after ACL injury if typical patient referral patterns are changed. Even for a highly productive ACL practice it is imperative to involve PCPs, Surgeons and outreach physician providers as stake holders into the study. Early knee joint aspirations are well tolerated and can be performed consecutively without patient withdrawals. Patients report subjectively less pain after the aspirations. Few patients refuse enrollment. Strict inclusion criteria result in a low number of eligible patients (10–20% only). A careful pre-study analysis of referral patterns, patient capture and environment is critical to perform randomized clinical trials in this patient population.