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Painful loading of the knee during walking is a key feature of knee osteoarthritis (OA). The external knee moments derived from three-dimensional gait analysis represent dynamic knee loads and may help evaluate surgical interventions. However, the relationships between knee moments and pain and the effects of surgery remain unclear. The overall purpose of this thesis was to investigate knee moments and pain during walking in patients with moderate medial knee OA, including the effects of limb realignment and ligament reconstruction surgeries. This thesis includes three studies investigating knee moments in patients with medial compartment tibiofemoral OA. Chapter 2 describes a cross-sectional study examining the relationship between knee pain and knee moments during walking, while controlling for extraneous factors by comparing limbs within 265 patients with medial knee OA. Using conditional logistic regression, results indicated greater odds of an increase in pain during walking with increased knee adduction moment, adduction impulse and internal rotation moment, and decreased knee flexion moment. These findings suggest a strong relationship between knee moments (in all three planes of motion) and knee pain during walking when between-person confounding is lessened. Chapter 3 describes a prospective cohort study evaluating the bilateral changes in knee moments in all three planes of motion in 33 patients undergoing combined medial opening-wedge high tibial osteotomy (HTO) and anterior cruciate ligament (ACL) reconstruction (HTO-ACLR). Patients underwent three-dimensional gait analysis, patient-reported outcomes and radiographic analysis preoperatively, 2 years postoperatively and a minimum 5 years postoperatively. Results indicated significant reductions in the knee adduction and internal rotation moments in the surgical limb, and a decrease in the knee flexion moment and an increase in the knee extension moment in both limbs. Changes in only the surgical limb suggest that HTO-ACLR reduces frontal and transverse plane knee moments. Bilateral changes suggest the passage of time, rather than the surgery, is responsible for the changes in sagittal plane knee moments. Chapter 4 describes a retrospective matched cohort study comparing preoperative and 5-year postoperative changes in the knee adduction and flexion moments in 52 patients who underwent either combined HTO-ACLR or HTO-Alone. Results indicated that both groups experienced a significant reduction in the knee adduction moment in the surgical limb. However, the HTO-Alone group also experienced a significant decrease in the knee flexion moment while the HTO-ACLR group experienced no change in sagittal plane knee moments. These findings suggest that HTO-ACLR may lessen the long-term decrease in the knee flexion moment typically observed over time in patients with knee OA. Overall, the results of this thesis support the use of investigating bilateral knee moments during walking in patients with medial knee OA, and provide rationale for future research examining whether the biomechanical changes observed in these individuals affects OA progression.