180 patients diagnosed with knee OA were randomized to receive either an exercise intervention based on the McKenzie Mechanical Diagnosis and Therapy (MDT) system or no intervention (wait-list control), to compare pain and function. Additionally, an exploratory subgroup analysis was performed among exercise patients between those with a MDT derangement classification who received end-range exercises and those classified as a MDT nonresponder who received evidence based therapy. Results at 2 weeks and 3 months from the main analysis revealed a significant treatment effect, in addition to significantly better pain and function scores in the exercise intervention group compared to the control group. Subgroup analysis favoured patients with a MDT derangement classification over other groups.