Aspirin for Venous Thromboembolism Prevention in Orthopaedic Surgery with Focus on Trauma and Arthroplasty: A Structured Evidence-Based Review of Randomised Trials, Guidelines, and Contemporary Practice Considerations

Background: Venous thromboembolism (VTE) remains a clinically relevant complication following major orthopaedic procedures, particularly total hip arthroplasty (THA), total knee arthroplasty (TKA), and fracture surgery. Although low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs) are widely regarded as standard pharmacological options, aspirin (acetylsalicylic acid, ASA) has gained renewed attention because of its low cost, oral administration, and favourable bleeding profile. However, the available evidence is heterogeneous, and its interpretation is complicated by differences in patient selection, timing and duration of prophylaxis, diagnostic methodology, aspirin dosing regimens, and the increasing adoption of modern fast-track arthroplasty pathways. Methods: A structured evidence-based review was conducted in accordance with PRISMA 2020 principles. PubMed, Embase, Web of Science, and the Cochrane Library were searched through September 2025 for randomised controlled trials (RCTs), major international clinical practice guidelines, and selected high-level studies relevant to the interpretation of aspirin-based orthopaedic thromboprophylaxis. Nine RCTs, four major guideline documents, and sixteen additional Level I–II studies were included. Outcomes of interest were symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and mortality. Risk of bias was assessed using the Cochrane ROB 2 framework. Owing to marked methodological heterogeneity, no formal pooled meta-analysis was undertaken. Results: The available RCT evidence suggests that aspirin may perform adequately within structured sequential or risk-stratified prophylaxis strategies, but not in all clinical settings. In arthroplasty, EPCAT II demonstrated non-inferiority of aspirin when introduced after an initial five-day course of rivaroxaban, whereas CRISTAL showed higher early symptomatic VTE rates when aspirin was used as sole primary prophylaxis from postoperative day 0. Importantly, thromboembolic events in CRISTAL occurred earlier in the aspirin cohort, supporting the concept that anticoagulant therapy remains important during the immediate postoperative hypercoagulable phase. In trauma surgery, PREVENT CLOT established non-inferiority of aspirin compared with LMWH for 90-day mortality; however, the predominantly young study population and the inclusion of upper-extremity fractures limit extrapolation to elderly hip fracture patients. Several smaller RCTs reported no major differences between aspirin and anticoagulants, but these studies were frequently underpowered and relied on less sensitive diagnostic strategies. Historical and contemporary guidelines remain heterogeneous, and evidence from modern fast-track arthroplasty pathways suggests that current trial-based conclusions may not be directly generalisable to short-duration prophylaxis settings. Conclusions: Aspirin may have a role in orthopaedic thromboprophylaxis when used within structured, risk-adapted or sequential protocols, particularly in standard-risk arthroplasty patients and selected trauma populations. However, current evidence does not support its universal use as sole primary prophylaxis in major orthopaedic surgery, especially during the early postoperative hypercoagulable phase or in high-risk patients. Furthermore, the available literature does not permit definitive recommendations regarding the optimal aspirin dose or duration of prophylaxis. The generalisability of the existing literature is further limited by methodological heterogeneity and by the absence of RCTs directly evaluating ultra-short anticoagulant regimens versus prolonged aspirin prophylaxis in modern fast-track arthroplasty. Further high-quality, standardised trials are required.