This study examined the time-dependent course of the minimally clinically important difference (MCID) and the substantial clinical benefit (SCB) achievement for International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales following anterior cruciate ligament reconstruction (ACLR). A prospective institutional registry was queried for patients receiving ACLR. The patient-reported outcome measures (PROMs) of interest included the IKDC score and KOOS sub-scales. One hundred forty-three patients (mean±SD age, 30.86±12.78 years; mean±SD body mass index, 25.51±4.64 kg/m2) were included in the analysis. Threshold values for the MCID/SCB were 18.9 of 29.6 on IKDC score, 15.7 of 25.3 on KOOS Symptom, 11.9 of 15.5 on KOOS Pain, 13.3 of 20.0 on KOOS ADL, 25.9 of 35.8 on KOOS Quality of Life (QoL), and 27.0 of 43.0 on KOOS Sport (area under the curve, 0.74-0.91). Overall, MCID achievement rates increased from 28.0% to 42.7% at 6 months to 41.9% to 70.8% at 12 months. Achievement rates of SCB increased from 16.1% to 30.4% at 6 months to 29.3% to 51.8% at 12 months. Statistically significant increases in MCID achievement (chi-square=47.95-79.36, all P<.001) and SCB achievement (chi-square=26.02-53.24, all P<.001) occurred from preoperative to 6-month time points across PROMs. From 6-month to 12-month time points, increases in MCID achievement occurred on IKDC score and KOOS QoL (chi-square=5.53-15.11, P<.001-.009). Statistically significant increases in MCID and SCB achievement occurred from preoperative to 6-month time points across IKDC score and KOOS subscales; however, statistically significant increases in achievement rates from 6 months to 1 year occurred on IKDC score, KOOS QoL, and KOOS Sport. This study underlines the importance of considering psychological factors and rehabilitative milestones when examining the achievement MCID and SCB after ACLR. [Orthopedics. 2021;44(5):299-305.].