ACL injury prevention programs often involve strengthening the knee muscles. We posit that an unrecognized benefit of such training is the associated increase in the tensile stiffness of the hypertrophied muscle. We tested the hypothesis that an increased quadriceps tensile stiffness would reduce peak anteromedial bundle (AM-)ACL relative strain in female knees. Twelve female cadaver knees were subjected to compound impulsive two-times body weight loads in compression, flexion, and internal tibial torque beginning at 15˚flexion. Knees were equipped with modifiable custom springs to represent the nonlinear rapid stretch behavior of a normal and increased stiffness female quadriceps (i.e., 33% greater stiffness). Peak AM-ACL relative strain was measured using an in situ transducer while muscle forces and tibiofemoral kinematics and kinetics were recorded. A 3D ADAMS TM dynamic biomechanical knee model was used in silico to interpret the experimental results which were analyzed using a repeated-measures Wilcoxon test. Female knees exhibited a 16% reduction in peak AM-ACL relative strain and 21% reduction in change in flexion when quadriceps tensile stiffness was increased by 33% (mean (SD) difference: 0.97% (0.65%), p ¼ 0.003). We conclude that increased quadriceps tensile stiffness reduces peak ACL strain during a controlled study simulating a pivot landing. There are 300,000 anterior cruciate ligament (ACL) injuries in the United States each year, 1 with a disproportionate number of these injuries occurring in female athletes. 2,3 ACL injuries are a major public health concern because they are immediately disabling with high associated treatment costs, lost time, and the increased risk of developing early onset knee osteoarthritis. 4 ACL injury prevention programs aimed at reducing the number of injuries in female athletes often include exercises to strengthen the knee extensor muscles, including leg press, squatting, and lunge exercises. 5-9 However, the benefits of such exercises remain uncertain given limited success. 10 The muscles of female athletes may provide less resistance to knee joint shear and torsional loads than for male athletes. 11,12 Since females have 45% less active quadriceps stiffness than males, 13 peak ACL strain may be routinely higher in females. Indeed, Lipps et al. 14 showed that female knees equipped with a female quadriceps tensile stiffness value had 95% greater peak ACL strain than height-and weightmatched male knees equipped with 25% greater quadriceps tensile stiffness in simulated pivot landings.Muscle tensile stiffness can be increased by both muscle hypertrophy 15 as well as by increased muscle activation, 16 both of which can be affected by training targeting the innervation and size of the fibers within a muscle through expression of the AKT pathway 17 or inhibition of transforming growth factor-b signaling pathways. 18 Knee extensor strength training in humans will produce an increase in type II muscle fiber cross-sectional area within the vastus lateralis 19,20 as...