The aims of this case-control study were to: (1) Identify cartilage locations and volumes at risk of osteoarthritis (OA) using subject-specific finite element (FE) models; (2) Quantify the relationships between the simulated biomechanical parameters and T and T relaxation times of magnetic resonance imaging (MRI). We created subject-specific FE models for seven patients with anterior cruciate ligament (ACL) reconstruction and six controls based on a previous proof-of-concept study. We identified locations and cartilage volumes susceptible to OA, based on maximum principal stresses and absolute maximum shear strains in cartilage exceeding thresholds of 7 MPa and 32%, respectively. The locations and volumes susceptible to OA were compared qualitatively and quantitatively against 2-year longitudinal changes in T and T relaxation times. The degeneration volumes predicted by the FE models, based on excessive maximum principal stresses, were significantly correlated (r = 0.711, p < 0.001) with the degeneration volumes determined from T relaxation times. There was also a significant correlation between the predicted stress values and changes in T relaxation time (r = 0.649, p < 0.001). Absolute maximum shear strains and changes in T relaxation time were not significantly correlated. Five out of seven patients with ACL reconstruction showed excessive maximum principal stresses in either one or both tibial cartilage compartments, in agreement with follow-up information from MRI. Expectedly, for controls, the FE models and follow-up information showed no degenerative signs. Our results suggest that the presented modelling methodology could be applied to prospectively identify ACL reconstructed patients at risk of biomechanically driven OA, particularly by the analysis of maximum principal stresses of cartilage.