Appropriate muscular response following an external perturbation is essential in preventing falls. Transtibial prosthesis users lack a foot-ankle complex and associated sensorimotor structures on the side with the prosthesis. The effect of this lack on rapid responses of the lower limb to external surface perturbations is unknown. The aim of the present study was to compare electromyogram (EMG) response latencies of otherwise healthy, unilateral, transtibial prosthesis users (n = 23, mean +/- standard deviation [SD] age = 48 +/- 14 yr) and a matched control group (n = 23, mean +/- SD age = 48 +/- 13 yr) following sudden support-surface rotations in the pitch plane (toes-up and toes-down). Perturbations were elicited in various weight-bearing and limb-perturbed conditions. The results indicated that transtibial prosthesis users have delayed responses of multiple muscles of the lower limb following perturbation, both in the intact and residual limbs. Weight-bearing had no influence on the response latency in the residual limb, but did on the intact limb. Which limb received the perturbation was found to influence the muscular response, with the intact limb showing a significantly delayed response when the perturbation was received only on the side with a prosthesis. These delayed responses may represent an increased risk of falling for individuals who use transtibial prostheses.