PURPOSE: The purpose of this study was to assess the efficacy of aspirin versus low-molecular-weight heparin (LMWH) in preventing venous thromboembolism (VTE) following hip and knee arthroplasty. METHODS: PubMed/Medline, Embase, Cochrane Library and Google Scholar databases were searched from inception till June 2024 for original trials investigating the outcomes of aspirin versus LMWH in hip and knee arthroplasty. The primary outcome was VTE. Secondary outcomes included minor and major bleeding events, and postoperative mortality within 90 days. This review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 7 randomized controlled trials with 12,134 participants were included. The mean ages for the aspirin and LMWH cohorts were 66.6 (57.6-69.0) years and 66.8 (57.9-68.9) years, respectively. There was no statistically significant difference in the overall risk of VTE between the aspirin and the LMWH cohorts (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.48-1.89; p: 0.877). A subanalysis based on the specific VTE entity (pulmonary embolism [PE] or deep venous thrombosis) showed a significantly higher PE risk for patients receiving aspirin than the LMWH cohort (OR: 1.79; 95% CI: 1.11-2.89; p: 0.017). There was no difference in minor (OR: 0.64; 95% CI: 0.40-1.04; p: 0.072) and major bleeding (OR: 0.77; 95% CI: 0.40-1.47; p: 0.424) episodes across both groups. Furthermore, subanalysis among the total knee arthroplasty group showed that the aspirin cohort was significantly more likely to suffer VTEs than their LMWH counterparts (OR: 1.55; 95% CI: 1.21-1.98; p < 0.001). CONCLUSION: This study demonstrated a significantly higher risk of PE among patients receiving aspirin compared to LMWH following hip or knee arthroplasty for osteoarthritis. Aspirin was associated with a significantly higher overall VTE risk among patients undergoing knee arthroplasty, in particular. This might suggest the inferiority of aspirin compared to LMWH in preventing VTE following such procedures. LEVEL OF EVIDENCE: Level I.