Limb amputation and its adverse effects continue to pose significant public health problems in the United States and abroad. In the US, there are approximately 500 amputations performed every day. While this patient population continues to grow, currently-available prosthetic technologies and clinical care do not consistently return patients to the quality of life these individuals had pre-amputation. While many prior studies have focused on how the use of lowerlimb prostheses affect coordination of their ipsilateral and contralateral legs during gait, few seek to quantify the upstream effects at joints that are proximal to the amputation and do so in a systematic way that considers generalized (i.e., not task specific) end-limb loading. To better understand the challenges faced by individuals with transfemoral amputation, we designed a series of in silico studies to first apply forces at the distal end of the residual limb of varying magnitude and direction to compare how muscles that span the ipsilateral hip joint are recruited to stabilize the limb. In this Aim and those that follow, neuromusculoskeletal simulations were performed using two different models of limb amputation surgery (myodesis and myoplasty). In the second Aim, we identified how transfemoral amputation and generalized end-limb loading alter the joint reaction forces and moments of the lumbopelvic joint by simulating varying levels of residual femur abduction and end-limb force. In the final Aim of this research, we quantify how transfemoral amputation alters residual limb stability under varying end-limb forces. Collectively, we show that how amputated muscles within the residual limb are surgically reconstructed and recruited differs from those of intact unaltered musculature and able-bodied individuals. Our models suggest these muscles are less sensitive to end-limb force direction and that significant co-contraction of agonist and antagonistic muscle groups is required to stabilize the residual limb. We also suggest that myodes is amputation surgery can enhance the force production of amputated muscle groups, relative to myoplasty surgery. However, negative tradeoffs associated with frontal-plane limb stability and an overall profile of limb stability that is asymmetric arise with such musculotendon tension-preserving procedures. Regarding mechanical loading of the lower back, this work highlights how posterior and medially-directed end-limb forces, similar to those that would occur during the loading response phase of gait, causes lumbopelvic joint reaction forces to increase in an abnormal manner for individuals with transfemoral amputation, and that poor muscle anchoring (as studied by increasing residual femur abduction) exacerbate these issues. By using computerized neuromusculoskeletal models and dynamic simulations to systematically and thoroughly explore the internal biomechanical mechanisms at work in individuals with transfemoral amputation, these studies offer an avenue to inform surgical planning, prosthetic intervention and rehabilitation strategies for this patient population.