The myocutaneous anterolateral thigh (ALT) and vastus lateralis (VL) flaps include a large muscle mass and a sufficient vascular pedicle, and they have been used for decades to reconstruct traumatic and acquired defects of the head and neck and extremities. In spite of these benefits, musculoskeletal dysfunction was reported in nearly 1 out of 20 patients at follow-up. It is unclear whether the recently proposed muscle-sparing flap-raising approach could preserve VL muscle function and whether patients at increased risk could benefit from such an approach. Therefore, we performed a predictive dynamic gait simulation based on a biological motion model with gradual weakening of the VL during a self-selected and fast walking speed to determine the compensable degree of VL muscle reduction. Muscle force, joint angle, and joint moment were measured. Our study showed that VL muscle reduction could be compensated up to a certain degree, which could explain the observed incidence of musculoskeletal dysfunction. In elderly or fragile patients, the VL muscle should not be reduced by 50% or more, which could be achieved by muscle-sparing flap-raising of the superficial partition only. In young or athletic patients, a VL muscle reduction of 10%, which corresponds to a muscle cuff, has no relevant effect. Yet, a reduction of more than 30% leads to relevant weakening of the quadriceps. Therefore, in this patient population with the need for a large portion of muscle, alternative flaps should be considered. This study can serve as the first basis for further investigations of human locomotion after flap-raising.