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Background: Tibiofemoral anatomic parameters, such as tibial slope, femoral condyle shape, and anterior tibial subluxation, have been suggested to increase the risk of anterior cruciate ligament (ACL) reconstruction failure. However, such features have never been assessed among patients experiencing multiple failures of ACL reconstruction. Purpose: To compare the knee anatomic features of patients experiencing a single failure of ACL reconstruction with those experiencing multiple failures or with intact ACL reconstruction. Study: Case-control study; Level of evidence, 3. Methods: Twenty-six patients who experienced failure of revision ACL reconstruction were included in the multiple-failure group. These patients were matched to a group of 25 patients with failure of primary ACL reconstruction and to a control group of 40 patients who underwent primary ACL reconstruction with no failure at a minimum follow-up of 24 months. On magnetic resonance imaging (MRI), the following parameters were evaluated: ratio between the height and depth of the lateral and medial femoral condyles, the lateral and medial tibial plateau slopes, and anterior subluxation of the lateral and medial tibial plateaus with respect to the femoral condyle. The presence of a meniscal lesion during each procedure was evaluated as well. Anatomic, demographic, and surgical characteristics were compared among the 3 groups. Results: The patients in the multiple-failure group had significantly higher values of lateral tibial plateau slope (P < .001), medial tibial plateau slope (P < .001), lateral tibial plateau subluxation (P < .001), medial tibial plateau subluxation (P < .001), and lateral femoral condyle height/depth ratio (P = .038) as compared with the control group and the failed ACL reconstruction group. Moreover, a significant direct correlation was found between posterior tibial slope and anterior tibial subluxation for the lateral (r = 0.325, P = .017) and medial (r = 0.421, P < .001) compartments. An increased anterior tibial subluxation of 2 to 3 mm was present in patients with a meniscal defect at the time of the MRI as compared with patients who had an intact meniscus for both the lateral and the medial compartments. Conclusion: A steep posterior tibial slope and an increased depth of the lateral femoral condyle represent a common finding among patients who experience multiple ACL failures. Moreover, higher values of anterior subluxation were found among patients with repeated failure and those with a medial or lateral meniscal defect. [ABSTRACT FROM AUTHOR]