We present a new methodology to measure the running biomechanics of amputees. This methodology combines the use of a spring-mass model and symmetry index, two standard techniques in biomechanics literature, but not yet used in concert to evaluate amputee biomechanics. The methodology was examined in the context of a pilot study to examine two transtibial amputee sprinters and showed biomechanically quantifiable changes for small adjustments in prosthetic prescription. Vertical ground reaction forces were measured in several trials for two transtibial amputees running at constant speed. A spring-mass model was used in conjunction with a symmetry index to observe the effect of varying prosthetic height and stiffness on running biomechanics. All spring-mass variables were significantly affected by changes in prosthetic prescription among the two subjects tested (p < 0.05). When prosthetic height was changed, both subjects showed significant differences, in Deltay(max), Deltal and contact time (t(c)) on the prosthetic limb and in k(vert) and k(leg) on the sound limb. The symmetry indices calculated for spring-mass variables were all significantly affected due to changes in prosthetic prescription for the male subject and all but the peak force (F(peak)) for the female subject. This methodology is a straight-forward tool for evaluating the effect of changes to prosthetic prescription.