Background:Full-thickness chondral defects alter tibiofemoral joint homeostasis and, if left untreated, have the potential to progress to osteoarthritis.Purpose:To assess the effects of isolated and dual full-thickness chondral defect size and location on the biomechanical properties of the lateral femoral condyle (LFC) and medial femoral condyle (MFC) during dynamic knee flexion in goat knees without menisci.Methods:In 12 goat knees, we created progressively increasing full-thickness circular chondral defects (3-, 5-, and 7.5-mm diameter) in the weightbearing contact area of flexion and extension in the MFC, the LFC, or both. Each knee was fixed into a custom steel frame and attached to a motor with sensors inserted intra-articularly. For each testing condition, the knee was loaded to 100 N and underwent a dynamic range of motion between 90° of flexion and 30° of extension. The following parameters were collected: contact area, contact pressure, contact force, peak area, and peak pressure.Study Design:Controlled laboratory study.Results:The peak pressure at the defect rim of the MFC at full extension increased by 51.51% from no defect (1.887 MPa) to a 7.5-mm defect (2.859 MPa) (P < .001), and the peak pressure at the defect rim of the LFC at full extension increased by 139.14% from no defect (1.704 MPa) to a 7.5-mm defect (4.075 MPa) (P < .001). The peak pressures for LFC defects at all 3 diameters were significantly greater when compared with dual defects consisting of increasing LFC defect diameter and constant MFC defect diameter (P < .001 for all).Conclusion:Extremely large increases in peak pressure were seen at the rim of articular cartilage defects when evaluated under dynamic loading conditions. Isolated LFC defects experienced a greater increase in defect rim stress concentrations when compared with isolated MFC defects for equivalent increases in defect size. Defect size played a significant role independent of location for peak pressures on the MFC and LFC.Clinical Relevance:Significant rim-loading effects increase with defect size under dynamic loading and may result in increasingly rapid progression of articular cartilage lesions. Within the context of this goat model, findings suggest that lateral compartment chondral lesions are more likely to progress than medial compartment lesions of equivalent size.