BACKGROUND Medial femoral condyle (MFC) chondral defects cause knee pain. Clinical studies have shown worse functional outcomes and cartilage defect fill rates after microfracture in obese patients (BMI ≥30) and for defects with size ≥2 cm(2). PURPOSE To determine the effect of obesity, defect size, and cartilage thickness on the force sustained at the base of full-thickness MFC cartilage defects during weightbearing. STUDY DESIGN Controlled laboratory study. METHODS Eight human cadaveric knees were loaded in 15° of flexion. A sensor measured force across the medial compartment. The area at the base of the defect protected from load, termed the "area of containment," was quantified, and loads simulating weightbearing for BMIs of 20, 30, and 40 were applied. A full-thickness cartilage defect was created on the MFC. Cycles of loads were applied for defect sizes with diameters of 6, 8, 10, 12, 14, 16, 18, and 20 mm. A second sensor recorded force at the base of the defect for defects with diameters of 14, 16, 18, and 20 mm. RESULTS Loads simulating BMI ≥30 led to a decrease in the area of containment for all defects ≥14 mm in diameter (P ≤ .038). Base of defect force increased for defects ≥16 mm in diameter (area, ≥2 cm(2)) between loaded and unloaded states (P ≤ .042) and for loads simulating BMI ≥30 (P ≤ .045). Cartilage rim thickness <2 mm showed higher base of defect force than did thickness ≥2 mm, for all BMI groups (P ≤ .025). CONCLUSION Increased force at the base of MFC cartilage defects was observed for weightbearing loads simulating BMI ≥30, for defect size ≥2 cm(2), and for rim thickness <2 mm. This may lead to a biomechanically unfavorable environment after microfracture in these patient subsets. CLINICAL RELEVANCE These biomechanical findings corroborate clinical studies that have noted worse outcomes after microfracture in patients with BMI ≥30 and cartilage defects of size ≥2 cm(2). Further clinical studies are needed to compare microfracture with other cartilage restoration procedures in these patient subsets.