The purpose of this study was to explore the relationship between the forces applied to the starting blocks and the start performances (SPs) of amputee sprinters (ASs) and non-amputee sprinters (NASs). SPs of 154 male and female NASs (100-m personal records [PRs], 9.5814.00 s) and 7 male ASs (3 unilateral above knee, 3 unilateral below knee, 1 bilateral below knee; 100 m PRs, 11.7012.70 s) with running specific prostheses (RSPs) were analysed during full-effort sprint starts using instrumented starting blocks that measured the applied forces in 3D. Using the NAS dataset and a combination of factor analysis and multiple regression techniques, we explored the relationship between force characteristics and SP (quantified by normalized average horizontal block power). Start kinetics were subsequently compared between ASs and NASs who were matched based on their absolute 100 m PR and their 100 m PR relative to the world record in their starting class. In NASs, 86% of the variance in SP was shared with five latent factors on which measured parameters related to force application to the rear and front blocks and the respective push-off directions in the sagittal plane of motion were loaded. Mediolateral force application had little influence on SP. The SP of ASs was significantly reduced compared to that of NASs matched on the basis of relative 100-m PR (33.8%; d = 2.11, p < 0.001), while a non-significant performance reduction was observed when absolute 100-m PRs were used (17.7%; d = 0.79, p = 0.09). These results are at least partially explained by the fact that force application to the rear block was clearly impaired in the affected legs of ASs.