Purpose: To assess risk of cartilage loss in the tibiofemoral joint in relation to baseline damage severity, and to analyse the association of nearby pathologic findings on the risk of subsequent cartilage loss. Methods: The Multicenter Osteoarthritis Study is a longitudinal study of individuals with or at high risk for knee osteoarthritis. MRI examinations were assessed according to the Whole Organ MRI Score. Included were all knees with available baseline and 30 months MRIs. Ordinal logistic regression was used to estimate risk of cartilage loss in each subregion in relation to the number of associated articular features including bone marrow lesions, meniscal damage and extrusion and also in regard to baseline damage severity, respectively. Results: 13 524 subregions of 1365 knees were included. 3777 (27.9%) subregions exhibited prevalent cartilage damage at baseline and 1119 (8.3%) subregions showed cartilage loss at 30-month follow-up. Risk of cartilage loss was increased for subregions with associated features (OR 2.53, 95% CI 2.03 to 3.15 for one, 4.32 95% CI 3.42 to 5.47 for two and 5.30 95% CI 3.95 to 7.12 for three associated features; p for trend <0.0001). Subregions with prevalent cartilage damage showed increased risk for further cartilage loss compared to subregions with intact cartilage at baseline with small superficial defects exhibiting highest risk. Conclusions: Risk of cartilage loss is increased for subregions with associated pathology and further increased when more than one type of associated feature is present. In addition, prevalent cartilage damage increases risk for subsequent cartilage loss.