The main objective of this study is to determine the damage tolerance and to describe the damage mechanisms of the extended human knee when it is exposed to lateral impact loads in pedestrian accidents, particularly those that occur at high velocity. An experimental method for assessing the damage tolerance of the knee region to loads acting at the extended lower extremity was developed. In-Vitro experiments with human subjects were conducted where only the purest possible shearing deformation or the purest possible bending deformation affected the knee region at the time. Ten experiments at a velocity level of 40 km/h were performed in a shearing and a bending setup, respectively. The peak values of the shearing force and the bending moment related to the damage of knee ligaments and bone fractures were calculated at knee joint level. Damages were assessed by dissecting the lower extremity. In general, if the extremity was exposed to dynamic loads from high velocity impact, the main types of damage are fractures.When the knee joint was exposed to the “purest possible shearing deformation”, the most common initial damage mechanism was due to combination of shearing and bending deformation of the knee, which resulted in articular fractures and, related to them, ligament damage (40% of cases). Those fractures originated from development of axial compressive forces between femur and tibia condyles. This type of damage occurred when mean value of peak shearing force and peak bending moment acting at the knee joint level was 2.4 kN (SD 0.7) and 414 Nm (SD 96); the shearing displacement and bending angle was 16 mm (SD 7) and -3.0° (SD 1.6), respectively. Another common initial damage mechanism resulted in femur fractures (supracondylar or at the diaphysis). This type of damage occurred when mean value of peak shearing force and peak bending moment acting at the knee joint level was 2.9 kN (SD 0.3) and 501 Nm (SD 98), respectively. The corresponding shearing displacement at the knee was 28 mm (SD 2) and the bending angle was -2.5° (SD 1.8).When the knee joint was exposed to the “purest possible bending deformation” the most common initial damage mechanism (70% of cases) was related to the femur fractures (supracondylar or at the diaphysis). The mean value of peak shearing force and peak bending moment calculated at the knee joint level when these fractures occurred was 1.4 kN (SD 0.6) and 351 Nm (SD 89), respectively. This type of initial damage occurred when the undamaged knee was already bent 16.4° (SD 4.4). The initial ligament damage due to bending deformation of the knee was observed in 20% of cases only. The mean value of peak shearing force and peak bending moment developed at the knee joint level that correspond to ligament damage was 1.4 kN (SD 0.2) and 284 Nm (SD 18), respectively. This type of damage occurred when the knee was bent 14.6° (SD 0.2).