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There is increased interest in understanding the preoperative determinants of postoperative outcomes. Return to play (RTP) and the patient-reported minimal clinically important difference (MCID) are useful measures of postoperative outcomes after anterior cruciate ligament reconstruction (ACLR).To define the MCID after ACLR and to investigate the role of preoperative outcome scores for predicting the MCID and RTP after ACLR.Case-control study; Level of evidence, 3.There were 294 active athletes enrolled as part of an institutional ACL registry with a minimum 2-year follow-up who were eligible for inclusion. A questionnaire was administered to elicit factors associated with RTP. Patient demographic and clinical data as well as patient-reported outcome measures were captured as part of the registry. Outcome measures included the International Knee Documentation Committee (IKDC) subjective knee evaluation form, Lysholm scale, and 12-Item Short Form Health Survey (SF-12) physical component summary (PCS) and mental component summary (MCS). Preoperative outcome score thresholds predictive of RTP were determined using a receiver operating characteristic (ROC) with area under the curve (AUC) analysis. The MCID was calculated using a distribution-based method. Multivariable logistic models were fitted to identify predictors for achieving the MCID and RTP.At a mean (±SD) follow-up of 3.7 ± 0.7 years, 231 patients were included from a total 294 eligible patients. The mean age and body mass index were 26.7 ± 12.5 years and 23.7 ± 3.2 kg/m2, respectively. Of the 231 patients, 201 (87.0%) returned to play at a mean time of 10.1 months. Two-year postoperative scores on all measures were significantly increased from preoperative scores (IKDC: 50.1 ± 15.6 to 87.4 ± 10.7; Lysholm: 61.2 ± 18.1 to 89.5 ± 10.4; SF-12 PCS: 41.5 ± 9.0 to 54.7 ± 4.6; SF-12 MCS: 53.6 ± 8.1 to 55.7 ± 5.7; P < .001 for all). The corresponding MCID values were 9.0 (IKDC), 10.0 (Lysholm), 5.1 (SF-12 PCS), and 4.3 (SF-12 MCS). Preoperative score thresholds predictive of RTP were the following: IKDC, 60.9; Lysholm, 57.0; SF-12 PCS, 42.3; and SF-12 MCS, 48.3. These thresholds were not independently predictive but achieved significance as part of the multivariable analysis. In the multivariable analysis for RTP, preoperative SF-12 PCS scores above 42.3 (odds ratio [OR], 2.73; 95% CI, 1.09-7.62) and SF-12 MCS scores above 48.3 (OR, 4.41; 95% CI, 1.80-10.98) were predictive for achieving RTP; an ACL allograft (OR, 0.26; 95% CI, 0.06-1.00) was negatively predictive of RTP. In the multivariable analysis for the MCID, patients with higher preoperative scores were less likely to achieve the MCID (P < .0001); however, a higher preoperative SF-12 MCS score was predictive of achieving the MCID on the IKDC form (OR, 1.27; 95% CI, 1.11-1.52) and Lysholm scale (OR, 1.08; 95% CI, 1.00-1.16). Medial meniscal injuries, older age, and white race were also associated with a decreased likelihood for achieving the MCID.Preoperative SF-12 MCS and PCS scores were predictive of RTP after ACLR; patients scoring above 42.3 on the SF-12 PCS and 48.3 on the SF-12 MCS were more likely to achieve RTP. Additionally, we defined the MCID after ACLR and found that higher SF-12 MCS scores were predictive of achieving the MCID on knee-specific questionnaires.