Abstract Purpose We performed a phase 2 randomized clinical trial to evaluate the preliminary effectiveness of a clinic-based patellar mobilization therapy (PMT) in patients with knee osteoarthritis. Methods We recruited 208 patients with knee osteoarthritis at primary care clinics in Hong Kong. Patients were randomly assigned (1:1) to the intervention group or the control group. The intervention group received 3 PMT treatment sessions from primary care physicians at 2-month intervals, with concomitant prescription of a home-based vastus medialis oblique muscle exercise. The control group received PMT after the study period. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Secondary outcomes included the WOMAC composite, function, and stiffness scores; the visual analog scale score for pain; objective physical function tests (30-s chair stand, 40-m walk test, timed up and go test, and EuroQol-5D). All outcomes were evaluated at baseline and at 24 weeks through intention-to-treat analysis. Results We observed no baseline between-group differences. The WOMAC pain score showed greater improvement in the intervention group than in the control group at 24 weeks (between-group difference −15.6, 95% Cl, −20.5 to −10.7, P <.001). All secondary outcomes also demonstrated significant between-group differences. Conclusions Patellar mobilization therapy has the potential to reduce pain and improve function and quality of life for patients with knee osteoarthritis. Future clinical trials with comparison to other active comparator controls will help determine the overall efficacy and facilitate the deployment of PMT in real-world practice.