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Objective: To test the effectiveness of a 32-week, stepped-care intervention on disease remission rates in overweight and obese patients with medial tibiofemoral osteoarthritis (OA) compared to controls., Methods: In this randomized controlled trial, eligible participants were ≥50 years of age with a body mass index of ≥28 kg/m 2 and radiographic evidence of medial tibiofemoral OA. Participants were randomized to stepped-care (n = 87) or control group (n = 84). The stepped-care group received a 2-step intervention. The first step consisted of an 18-week diet and exercise program. The second step consisted of 4 treatment subgroups: 1) diet and exercise maintenance; 2) cognitive-behavioral therapy; 3) unloader knee brace; and 4) muscle strengthening exercises. Allocation into subgroups was based on disease remission state and clinical characteristics. The primary end point was the disease remission rate (yes/no) at 32 weeks, which was reached when participants achieved the Patient Acceptable Symptom State cutoff value for pain and for the patient global assessment of disease activity and/or functional impairment., Results: Disease remission at 32 weeks was achieved by 18 of 68 (26%) in the control group and 32 of 82 (39%) in the stepped-care group (difference 12.6% [95% confidence interval -2.3, 27.4], P = 0.10). The stepped-care group showed an improvement in pain and function between baseline and 20 weeks. While functional improvement was maintained at 32 weeks, pain levels tended to get worse between weeks 20 and 32., Conclusion: The proposed intervention did not promote a significant difference in the rate of disease remission in comparison to the control group for overweight or obese patients with medial tibiofemoral OA., (© 2020, American College of Rheumatology.)