Background. No effective cure exists for knee osteoarthritis (OA). Low-burden self-management strategies that can slow disease progression are needed. Bone marrow lesions (BMLs) are a source of knee pain and accelerate cartilage loss. Importantly, they may be responsive to biomechanical off-loading treatments. Objective. The study objective is to investigate whether, in people with medial tibiofemoral OA, daily cane use for 12 weeks reduces the volume of medial tibiofemoral BMLs and improves pain, physical function, and health-related quality of life. Design. This study will be an assessor-masked, 2-arm, parallel-group, multisite randomized controlled trial. Setting. The community will serve as the setting for this study. Participants. The study participants will be people who are 50 years old or older and have medial tibiofemoral OA and at least 1 medial tibiofemoral BML. Intervention. The participants will be allocated to either the cane group (using a cane daily whenever walking for 12 weeks) or the control group (not using any gait aid for 12 weeks). Measurements. Outcomes will be measured at baseline and 13 weeks. The primary outcome will be total medial tibiofemoral BML volume measured from magnetic resonance imaging. Secondary outcomes will include BML volume of the medial tibia and/or femur, knee pain overall and on walking, physical function, participant-perceived global change, and health-related quality of life. Additional measures will include physical activity, coint-erventions, adverse events, participation, participant demographics, cane training process measures and feasibility, barriers to and facilitators of cane use, and loss to follow-up. Limitations. People who are morbidly obese will not be included because of difficulties with magnetic resonance imaging. Conclusions. The findings of this study will help to determine whether cane use can alter disease progression in people with medial tibiofemoral OA and/or influence clinical symptoms. This study may directly influence clinical guidelines for the management of knee OA.