Aspirin-Based Thromboprophylaxis Versus Anticoagulant Regimens After Total Hip or Knee Arthroplasty: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Objectives: Aspirin is widely used for venous thromboembolism prophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA); however, uncertainty remains regarding its efficacy and safety compared with anticoagulant regimens. This systematic review and meta-analysis evaluated aspirin-based thromboprophylaxis versus anticoagulant regimens following THA or TKA. Materials and Methods: PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched through July 2026 for randomized controlled trials comparing aspirin-based prophylaxis with anticoagulant regimens. The primary outcomes were any deep vein thrombosis (DVT), symptomatic DVT, and symptomatic venous thromboembolism (VTE). Secondary outcomes included pulmonary embolism (PE), proximal and distal DVT, bleeding outcomes, wound complications, blood transfusion, and mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Additional risk-difference sensitivity analyses incorporated CRISTAL’s published cluster-adjusted estimates. Results: Sixteen trials involving 21,265 participants were included. Aspirin was associated with higher risks of symptomatic DVT (RR 1.79, 95% CI 1.35–2.38), symptomatic VTE (RR 1.70, 95% CI 1.33–2.18), PE (RR 1.89, 95% CI 1.33–2.68), and distal DVT (RR 1.47, 95% CI 1.06–2.06). Aspirin was associated with lower risks of minor bleeding (RR 0.47, 95% CI 0.31–0.71) and ecchymosis or bruising (RR 0.60, 95% CI 0.39–0.93). No statistically significant differences were detected for the other assessed outcomes. Additional analyses incorporating CRISTAL’s cluster-adjusted risk differences did not identify statistically significant differences for the three primary outcomes or PE. Conclusions: The main pooled analyses associated aspirin-based thromboprophylaxis with higher risks of symptomatic thromboembolic events. However, the symptomatic DVT and symptomatic VTE associations were no longer statistically significant after exclusion of CRISTAL or restriction to trials at low risk of bias. The low-risk analysis identified a significantly higher risk of any DVT with aspirin. Aspirin reduced minor bleeding and bruising without a statistically significant reduction in major or clinically relevant non-major bleeding. These findings require cautious interpretation given dependence on CRISTAL, sensitivity to trial inclusion and analytical approach, and differences in prophylactic strategies and outcome definitions.