The aim of this study is to compare the efficacy and safety of aspirin and low-molecular-weight heparin (LMWH) in preventing thromboembolic events in patients with fractures. The present meta-analysis was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched EMBASE, PubMed, and EBSCO to find articles comparing aspirin and LMWH in patients with orthopedic trauma from inception to April 15, 2023. Limits were set to studies published in the English language only. Outcomes assessed in this meta-analysis included VTE and all-cause mortality. VTE can manifest as deep venous thrombosis (DVT) and pulmonary embolism. For safety analysis, rates of wound complication, infection, and bleeding complications were compared between the two study groups. A total of three studies were included in this meta-analysis enrolling 12884 patients. The study found no significant difference between the two groups in the risk of DVT and pulmonary embolism, and aspirin was non-inferior to LMWH for the prevention of all-cause mortality in patients. Additionally, no significant safety risk was associated with aspirin thromboprophylaxis. These findings suggest that inexpensive over-the-counter aspirin is as effective as LMWH in terms of safety and efficacy profile, making it a feasible option to consider in clinical practice.