['To investigate compositional cartilage changes measured with 3T MRI-based T2 values over 48 months in overweight and obese individuals with different degrees of weight loss (WL) and to study whether WL slows knee cartilage degeneration and symptom worsening.', 'We studied participants from the Osteoarthritis Initiative with risk factors or radiographic evidence of mild to moderate knee osteoarthritis with a baseline BMI ≥25\xa0kg/m(2). We selected subjects who over 48 months lost a, moderate (BMI change, 5-10%WL, n\xa0=\xa0180) or large amount of weight (≥10%WL, n\xa0=\xa078) and frequency-matched these to individuals with stable weight (<3%, n\xa0=\xa0258). Right knee cartilage T2 maps of all compartments and grey-level co-occurrence matrix (GLCM) texture analyses were evaluated and associations with WL and clinical symptoms (WOMAC subscales for pain, stiffness and disability) were assessed using multivariable regression models.', 'The amount of weight change was significantly associated with change in cartilage T2 of the medial tibia (β 0.9\xa0ms, 95% CI 0.4 to 1.1, P\xa0=\xa00.001). Increase of T2 in the medial tibia was significantly associated with increase in WOMAC pain (β 0.5\xa0ms, 95% CI 0.2 to 0.6, P\xa0=\xa00.02) and disability (β 0.03\xa0ms, 95% CI 0.003 to 0.05, P\xa0=\xa00.03). GLCM contrast and variance over all compartments showed significantly less progression in the >10%WL group compared to the stable weight group (both comparisons, P\xa0=\xa00.04).'] Is progression of cartilage degeneration and clinical symptoms in obese and overweight individuals dependent on the amount of weight loss : 48-month data from the Osteoarthritis Initiative?