This study examined the effects of speed and leg prostheses on mediolateral (ML) foot placement and its variability in sprinters with and without transtibial amputations. We hypothesized that ML foot placement variability would: 1. increase with running speed up to maximum speed and 2. be symmetrical between the legs of non-amputee sprinters but asymmetrically greater for the affected leg of sprinters with a unilateral transtibial amputation. We measured the midline of the body (kinematic data) and center of pressure (kinetic data) in the ML direction while 12 non-amputee sprinters and 7 Paralympic sprinters with transtibial amputations (6 unilateral, 1 bilateral) ran across a range of speeds up to maximum speed on a high-speed force measuring treadmill. We quantified ML foot placement relative to the body's midline and its variability. We interpret our results with respect to a hypothesized relation between ML foot placement variability and lateral balance. We infer that greater ML foot placement variability indicates greater challenges with maintaining lateral balance. In non-amputee sprinters, ML foot placement variability for each leg increased substantially and symmetrically across speed. In sprinters with a unilateral amputation, ML foot placement variability for the affected and unaffected leg also increased substantially, but was asymmetric across speeds. In general, ML foot placement variability for sprinters with a unilateral amputation was within the range observed in non-amputee sprinters. For the sprinter with bilateral amputations, both affected legs exhibited the greatest increase in ML foot placement variability with speed. Overall, we find that maintaining lateral balance becomes increasingly challenging at faster speeds up to maximum speed but was equally challenging for sprinters with and without a unilateral transtibial amputation. Finally, when compared to all other sprinters in our subject pool, maintaining lateral balance appears to be the most challenging for the Paralympic sprinter with bilateral transtibial amputations.