The aims of this study were to predict and explain the patterns of ligament forces in the stump of a left trans-tibial amputee during walking, and to study the effects of the prosthetic alignment. Musculoskeletal modeling and computer simulation were combined to calculate ligament forces. The prosthesis was aligned to be in optimal position for the subject and then changed by +/-6 degrees in the sagittal plane. The results showed most ligaments bearing the maximum tension forces around both heel-strike and toe-off. The PT force was the biggest in all of the ligaments which were studied. The load patterns of ACL and PCL were opposite in the gait cycle, but the load patterns of MCL and LCL appeared similar. The above results showed that the ligament forces increased at the incorrect alignment, because the incorrect alignment could break the relative translation of the femur and tibia, and that would generate the extra ligament strains. As a result, the ligament forces increased, and the long-duration fatigue occurred more easily. This finding suggests that the proper prosthetic alignment is very important for the normal activities of the stump ligaments.