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Background: Interest in the role of lateral extra-articular tenodesis (LET) in preventing rotatory instability and the pivot-shift phenomenon after anterior cruciate ligament reconstruction (ACLR) has been recently renewed. Nevertheless, there is still concern about overconstraint of the lateral compartment of the knee and the risk of subsequent osteoarthritis (OA). Purpose: The purpose of this retrospective study was to compare long-term subjective and objective outcomes and the rate of OA development between patients undergoing isolated ACLR (iACLR) with a hamstring tendon autograft and those with a combined Arnold-Coker modification of the McIntosh extra-articular procedure. Risk factors for long-term OA were evaluated. Study Design: Cohort study; Level of evidence, 3. Methods: The study included 165 consecutive patients treated at a single center by ACLR. A total of 86 patients underwent iACLR (iACLR group) and 79 received combined intra- and extra-articular reconstruction (ACLR+LET). The International Knee Documentation Committee (IKDC), Lysholm, and Tegner activity scores were administered. Knee stability was tested through the Lachman test, the pivot-shift test, and the KT-1000 knee arthrometer test. A positive pivot-shift test (++/+++), laxity on the KT-1000, and referred giving-way episodes or revision ACLR were considered failures. Radiographic results were assessed according to the Fairbank, IKDC, and Kellgren-Lawrence scales. Radiographic evaluation included both the overall tibiofemoral joint and the medial and lateral compartment separately. A univariate and a multivariate logistic regression with penalized maximum likelihood was used to identify risks factors associated with long-term OA. Results: The mean follow-up was 15.7 years. There were no statistically significant differences in subjective scores between the 2 groups. A side-to-side difference >5 mm on the KT-1000 arthrometer evaluation was found in 8 patients in the iACLR group and in 1 patient in the ACLR+LET group ( P = .01). Nine cases of failure were found in the iACLR group and only 1 case was found in the ACLR+LET group ( P = .0093). Patients in the iACLR group had a significantly higher OA grades than those in the ACLR+LET group for the overall tibiofemoral joint and the lateral compartment of the knee. No differences were found in the medial compartment. A higher level of lateral compartment OA was found in patients who received partial lateral meniscectomy in the iACLR group compared with those in the ACLR+LET group. Univariate and multivariate analysis results demonstrated that meniscectomy was the most significant factor for long-term OA development. Conclusion: A significantly higher risk of long-term OA was found with iACLR than with ACLR combined with the Arnold-Coker modification of the McIntosh extra-articular procedure. Knees with combined ACLR also had a significantly lower OA grade after partial lateral meniscectomy. Additionally, those undergoing combined ACLR had better knee stability and lower graft rupture rates at the long-term follow-up. Partial meniscectomy was the main risk factor negatively associated with OA changes.