The effects of seatbelt use, muscle tension, lower-extremity posture, driver fore-aft seat position, seat height, and seat angle on the likelihood of knee, thigh, and hip (KTH) injuries during knee-to-knee-bolster impacts in frontal crashes were studied using a finite element (FE) human model. A midsize male whole-body FE model, with a previously validated knee-impact response, was further validated in this study against whole-body responses from two sets of cadaver sled tests. This human model was integrated with vehicle instrument panel, seat, and restraint-system models. An FMVSS 208 crash pulse of a passenger car was used to evaluate the effects of the aforementioned factors on the risk of KTH injuries. Simulation results indicated that seatbelts significantly reduced peak forces generated at the knee, in the thigh, and at the hip, and thereby reduced the risk of KTH injuries. Lower-extremity muscle tension significantly increased compressive force in the femur but not at the knee or hip. Abducting the hip (i.e., increasing thigh splay) significantly decreased peak forces at the knee, thigh, and hip relative to a neutral or adducted posture. More rearward seating positions produced significantly higher forces at the knee and hip for unbelted drivers, but significantly lower peak forces at the knee and hip for belt-restrained drivers. More inclined seat angles generally reduced peak force at all locations in the KTH, but the reductions are not statistically significant.