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Objective: To identify risk factors for radiographic signs of post-traumatic osteoarthritis (OA) 2-3 years after anterior cruciate ligament (ACL) reconstruction through multivariable analysis of minimum joint space width (mJSW) differences in a specially designed nested cohort., Methods: A nested cohort within the Multicenter Orthopaedic Outcomes Network (MOON) cohort included 262 patients (148 females, average age 20) injured in sport who underwent ACL reconstruction in a previously uninjured knee, were 35 or younger, and did not have ACL revision or contralateral knee surgery. mJSW on semi-flexed radiographs was measured in the medial compartment using a validated computerized method. A multivariable generalized linear model was constructed to assess mJSW difference between the ACL reconstructed and contralateral control knees while adjusting for potential confounding factors., Results: Unexpectedly, we found the mean mJSW was 0.35 mm wider in ACL reconstructed than in control knees (5.06 mm (95% CI 4.96-5.15 mm) vs 4.71 mm (95% CI 4.62-4.80 mm), P < 0.001). However, ACL reconstructed knees with meniscectomy had narrower mJSW compared to contralateral normal knees by 0.64 mm (95% C.I. 0.38-0.90 mm) (P < 0.001). Age (P < 0.001) and meniscus repair (P = 0.001) were also significantly associated with mJSW difference., Conclusion: Semi-flexed radiographs can detect differences in mJSW between ACL reconstructed and contralateral normal knees 2-3 years following ACL reconstruction, and the unexpected wider mJSW in ACL reconstructed knees may represent the earliest manifestation of post-traumatic osteoarthritis and warrants further study., (Copyright © 2015. Published by Elsevier Ltd.)