Background <p>Novel oral anticoagulants (NOACs), including rivaroxaban, apixaban, edoxaban and dabigatran, are increasingly used for orthopaedic surgery patients. The aim of this study was to evaluate the efficacy and safety of NOACs in preventing venous thromboembolism (VTE) among patients with lower limb fractures.</p> Materials and methods <p>This meta-analysis included randomized controlled trials (RCTs). The PubMed, Embase, Cochrane Library, and Web of Science databases were comprehensively searched from inception to November 27, 2024. We evaluated the risk of bias via the Cochrane Risk of Bias Tool 2.0 (RoB 2.0). The efficacy outcomes focused on VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE), and the safety outcomes focused on major bleeding events. Two researchers screened the literature on the basis of the inclusion and exclusion criteria, evaluated the quality of the included studies, extracted the data, and conducted a meta-analysis using RevMan 5.4.1.</p> Results <p>The systematic search yielded 2,873 unique citations after deduplication. Ultimately, five RCTs involving 4,092 participants (2,066 participants in the NOAC group (rivaroxaban and edoxaban) and 2,026 participants in the LMWH group) were included. Pooled analysis revealed that NOACs reduced the incidence rate of DVT [OR = 0.48, 95% CI (0.23–0.97), <i>P</i> = 0.04; I²=10%]. However, there was no significant difference in the incidence of VTE [OR = 0.42, 95% CI (0.16–1.11), <i>P</i> = 0.08; I²=34%], PE [OR = 0.33, 95% CI (0.05–2.08), <i>P</i> = 0.24; I²=0%] or major bleeding [OR = 1.01, 95% CI (0.57–1.77), <i>P</i> = 0.98; I²=0%] between the LMWH group and the NOACs group.</p> Conclusions <p>Compared with LMWH, NOACs were associated with a lower risk of DVT in patients with lower limb fractures, although there was no statistically significant difference in preventing VTE, PE and major bleeding.</p> Clinical trail number <p>No. CRD42024619453.</p>