Abstract-Considering transtibial amputation (TTA) rehabilitation costs and complexity, high-quality literature should inform clinical practice. Systematic reviews (SRs) suggest this is not the case. This article's purpose was to review the highest-quality evidence available to guide clinical practice for TTA regarding five prosthetic intervention areas. Six databases were searched for high-quality SRs and prospective clinical trials (randomized clinical trials [RCTs]). Reviewers screened, sorted, rated (i.e., methodologic quality, bias risk), and extracted article data. Meta-analyses were conducted when possible. Thirty-one references were included (25 RCTs and 6 SRs). Five topical areas emerged (alignment, feet and ankles, interface, postoperative care, pylons). Twenty-three evidence statements were supported by level 2 evidence and eight by level 1 evidence. All RCTs reported randomization and reasonable data presentation. Concealed allocation and blinding were not widely used. Mean attrition was 11%. SRs included no meta-analyses. Functional level was poorly reported. Grouping feet and ankle components by functional classification enabled meta-analyses, though variance was considerable given the small sample sizes. Prosthetic interventions are generally safe for TTAs. High-quality literature enabled formulation of evidence statements to support select clinical practice areas, though quantity was lacking. Thus, numerous topics related to TTA care lack rigorous evidence. Although blinding in prosthetic research requires increased funding and effort, it could greatly improve the methodologic quality of prosthetic research.Abbreviations: CI = confidence interval, ESAR = energy storing and release, EWA = early walking aid, FK = flexible keel, GRF = ground reaction force, MA = multi-axial, NIH = National Institutes of Health, PEDro = Physiotherapy Evidence Database Scale, PTB = patella tendon bearing, RRD = rigid removable dressing, SA = single axis, SACH = solid ankle cushion heel, SIGN = Scottish Intercollegiate Guidelines Network, SR = systematic review, TSB = total surface bearing, TTA = transtibial amputation, VASS = vacuum-assisted suspension system, vGRF = vertical ground reaction force, VSP = vertical shock pylon.