ABSTRACT Restoring quadriceps muscle strength following anterior cruciate ligament reconstruction (ACLR) may help prevent the post-traumatic knee osteoarthritis that affects over 50% of knees 10-20 years after surgical reconstruction. However, a fundamental gap exists in our understanding of how to maximize muscle strength following ACLR, as current rehabilitation fails to restore symmetrical quadriceps strength. Our pilot work shows that when patients return to activity, quadriceps strength is ~70% of the uninjured side, which is far below the recommended 90%. Further, our data suggest that embedding high-intensity neuromuscular electrical stimulation (NMES) and eccentric exercise into standard of care ACL rehabilitation leads to higher quadriceps strength when compared with standard of care alone. However, the true efficacy of these interventions is unknown, as we currently lack controlled trials with adequate sample sizes. The absence of this information serves as the driving force and focus of the proposed trial. Therefore, we propose a double- blind randomized controlled trial where ACLR patients will be randomized to 1 of 4 arms. Study arms will include: 1) 8 weeks of NMES+8 weeks of eccentric exercise; 2) 8 weeks of NMES placebo+8 weeks of eccentric exercise; 3) 8 weeks of NMES+8 weeks of eccentric placebo; and 4) 8 weeks of NMES placebo+8 weeks of eccentric placebo. All study arms will receive standard of care ACL rehabilitation in addition to the study interventions. We hypothesize that subjects receiving NMES+eccentric exercise (Arm 1) will realize greater improvements in strength and biomechanical function at 6 months following ACLR than patients in the other 3 study arms. Further, we anticipate that patients in the NMES+eccentric exercise arm (Arm 1) will best eliminate negative changes in cartilage health at 18 months following ACLR. This study is innovative, because it employs interventions that directly target the primary mechanisms that result in strength loss following ACLR and will also evaluate whether improving muscle strength can minimize early changes in cartilage health, which may be indicative of future osteoarthritis. The proposed research is significant because it will identify evidence-based treatment approaches that can successfully counteract the muscle weakness which plagues ACLR patients for years after injury and contributes to the onset of post-traumatic osteoarthritis.