STUDY DESIGN Controlled longitudinal laboratory study. therapy (Pre-sx) and 6 months after ACLR (6mo). Repeated steps analysis of variance models were used to determine whether limb asymmetries changed differently over time in men and women. RESULTS Significant time x limb x sex interactions were recognized for hip and knee excursions and internal knee extension moments (P≤.007). Both sexes exhibited smaller knee excursions around the involved compared to the uninvolved knee at each time point (P≤.007) but only women demonstrated a decrease in the involved knee excursion from pre-sx to 6mo (P=.03). Women also exhibited smaller hip excursions (P<.001) and internal knee extension moments (P=.005) around the involved limb compared to the uninvolved limb at 6mo. Men exhibited smaller hip excursions and knee moments around the involved limb compared to the CD177 uninvolved limb (main effects P<.001). CONCLUSION The persistence of limb asymmetries in men and women 6 months after ACLR indicates that current rehabilitation efforts are inadequate for some individuals following ACLR. Keywords: ACL sex differences gait physical therapy Knee injuries predominate in sports11 and rupture of the anterior cruciate ligament (ACL) is one of the most common knee injuries.32 The number of ACL injuries sustained by males is greater than that Atractylenolide I of their female counterparts;21 however when comparing rate of injury in the same sports females’ risk for ACL injury is several times greater than males.3 5 40 Women not only demonstrate poorer function after ACL injury 17 29 but they are also less Atractylenolide I likely to return to sports after ACL reconstruction (ACLR) compared to men 4 8 17 and are at significantly greater risk of sustaining a second ACL injury if they do return to sports.8 37 46 Once representative of less than 10% of the high school athletic populace female athletes now account for 42% of high school sports participants whose total current populace is nearly 7.7 million.6 As the number of women participating in vigorous sporting activities continues to rise steadily and the incidence of ACL ruptures raises correspondingly effective rehabilitation management of ACL injuries is of critical importance. Sex influences knee function4 and second ACL injury risk following ACL reconstruction.37 Biomechanical asymmetries during a drop-jump task accurately predict future second ACL injury 37 but important changes in mechanics likely occur long before assessments of jumping tasks are safe. Walking gait mechanics are sensitive to changes following ACL injury43 and reconstruction23 42 and may allow for early identification of risky biomechanics. Kinematic and kinetic asymmetries of the hip and knee are associated with reduced functional performance at the time of return to sport clearance.15 Importantly alterations in the lower extremity biomechanics of athletes following ACLR exist in both limbs.9 12 15 22 35 39 41 Reduced joint motion and internal extension moments of the involved knee are common for many months following surgery 22 41 but can Atractylenolide I also be accompanied by altered joint kinetics of the contralateral knee and hip.22 39 41 Post-operative guidelines emphasize bilateral limb training Atractylenolide I 1 34 yet despite supervised rehabilitation and medical clearance to return to activity abnormal neuromuscular strategies persist.9 39 41 45 Evaluation of adaptations at the hip and knee in response to rehabilitation and ACLR and whether these changes are sex-specific will ultimately help refine evidence-based clinical care and return to sport decision-making. Rehabilitation which includes neuromuscular training elicits positive effects on dynamic knee function18 20 28 and movement patterns10 16 of athletes with ACL deficiency. Women in particular may have the most to gain from targeted pre-operative training. Women who sustain an ACL injury are more likely to report knee instability and significant functional disability29 and have also exhibited altered hip and knee mechanics which were not recognized in men.16 Progressive strength training and neuromuscular re-education successfully reduced the kinematic and kinetic asymmetries of the knee and hip in this small cohort of women after acute ACL injury 16 but whether these short-term improvements in gait mechanics gained prior to surgery persist.