Background: The soft tissue of the residual limb in transtibial prosthetic users encounters unique biomechanical challenges. Although not intended to tolerate high loads and deformation, it becomes a weight-bearing structure within the residuum-prosthesis-complex. Consequently, deep soft tissue layers may be damaged, resulting in Deep Tissue Injury (DTI). Whilst considerable effort has gone into DTI research on immobilised individuals, only little is known about the aetiology and population-specific risk factors in amputees. This scoping review maps out and critically appraises existing research on DTI in lower-limb prosthetic users according to (1) the population-specific aetiology, (2) risk factors, and (3) methodologies to investigate both. Results: A systematic search within the databases Pubmed, Ovid Excerpta Medica, and Scopus identified 16 English-language studies. The results indicate that prosthetic users may be at risk for DTI during various loading scenarios. This is influenced by individual surgical, morphological, and physiological determinants, as well as the choice of prosthetic componentry. However, methodological limitations, high inter-patient variability, and small sample sizes complicate the interpretation of outcome measures. Additionally, fundamental research on cell and tissue reactions to dynamic loading and on prosthesis-induced alterations of the vascular and lymphatic supply is missing. Conclusion: We therefore recommend increased interdisciplinary research endeavours with a focus on prosthesisrelated experimental design to widen our understanding of DTI. The results have the potential to initiate muchneeded clinical advances in surgical and prosthetic practice and inform future pressure ulcer classifications and guidelines.