Eighty-seven patients with chronic knee osteoarthritis were randomized to receive either cryoneurolysis (n=44) or a sham procedure (n=43). Both groups subsequently participated in an 8-week structured exercise program (GLA:D). The primary outcome was the difference in average pain over the previous 24 hours at 14 days post-intervention. Secondary outcomes included worst and least pain, pain during activity and rest, functional tests (e.g., chair stand, 40-m walk), isometric strength, and patient-reported outcomes (e.g., KOOS, EQ-5D, anxiety). Outcomes were assessed at baseline, 14 days, post-GLA:D, and at 6 and 12 months. Overall, the results revealed no significant difference in pain between groups at 14 days (primary endpoint), although minor improvements in least pain and walk time were noted in the cryoneurolysis group at 6 months. These effects were not sustained at 12 months. This suggests that the tested cryoneurolysis protocol does not confer a meaningful clinical benefit over sham in this population.