Total meniscectomies are commonly thought to cause progressive degenerative arthrosis pathology in articular cartilage in a period of a few years because of alteration of the biomechanical environment including increased joint instability. This concern has lead to a preference for partial meniscectomies, although lateral partial meniscectomies sometimes lead to catastrophic results. We performed a three-dimensional finite element model of the human tibiofemoral joint to examine the effect of lateral meniscectomy on knee biomechanics. The results were compared to those from modeling a medial meniscectomy. Under axial femoral compressive loads, the peak contact stress and maximum shear stress in the articular cartilage increased 200% more after a lateral than a medial meniscectomy. These increased stresses could partly explain the higher cartilage degeneration observed after a lateral meniscectomy.