OBJECTIVE Muscle strengthening exercises have been shown to improve pain and function in adults with mild-to-moderate knee osteoarthritis, but individual response rates can vary greatly. Predicting individuals who respond and those who do not is important in developing a more efficient and effective model of care for knee osteoarthritis (OA). Therefore, the purpose of this study was to use pre-intervention gait kinematics and patient-reported outcome measures to predict post-intervention response to a 6-week hip strengthening exercise intervention in patients with mild-to-moderate knee OA. METHODS Thirty-nine patients with mild-to-moderate knee osteoarthritis completed a 6-week hip-strengthening program and were subgrouped as Non-Responders, Low-Responders, or High-Responders following the intervention based on their change in Knee injury Osteoarthritis Outcome Score (KOOS). Predictors of responder subgroups were retrospectively determined from baseline patient-reported outcome measures and kinematic gait parameters in a discriminant analysis of principal components. A 3-4 year follow-up on 16 of the patients with knee OA was also done to examine long-term changes in these parameters. RESULTS A unique combination of patient-reported outcome measures and kinematic factors was able to successfully subgroup patients with knee osteoarthritis with a cross-validated classification accuracy of 85.4%. Lower patient-reported function in daily living (ADL) scores and hip frontal plane kinematics during the loading response were most important in classifying High-Responders from other sub-groups, while a combination of hip, knee, ankle kinematics were used to classify Non-Responders from Low-Responders. CONCLUSION Patient-reported outcome measures and objective biomechanical gait data can be an effective method of predicting individual treatment success to an exercise intervention. Measuring gait kinematics, along with patient-reported outcome measures in a clinical setting can be useful in helping make evidence-based decisions regarding optimal treatment for patients with knee OA.