Background <p>The prevalence of conditions necessitating anticoagulation therapy among pregnant women has been steadily increasing. Although low-molecular-weight heparin (LMWH) is commonly used, several studies have investigated the use of fondaparinux in pregnant women. However, the safety profile of fondaparinux in this population remains to be fully elucidated.</p> Methods <p>A comprehensive literature search across ten databases was conducted in September 2024. This meta-analysis was conducted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for systematic reviews of observational studies. Dichotomous data from eligible studies were combined using the Mantel‒Haenszel model. Standard mean differences with 95% confidence intervals were assessed. Heterogeneity was evaluated using I² statistics and the Cochran Q test, and the quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.</p> Results <p>Nine studies met the inclusion criteria. Based on the GRADE approach, the quality of evidence ranged from very low to low. Fondaparinux did not increase the incidence of bleeding-related adverse events (vaginal bleeding: OR = 0.99, 95% CI 0.43–2.30, <i>P</i> = 0.98; postpartum haemorrhage: OR = 0.35, 95% CI 0.07–1.73, <i>P</i> = 0.20). Fondaparinux was associated with reduced risks of hepatic transaminase elevation (OR = 0.20, 95% CI 0.08–0.49, <i>P</i> &lt; 0.01), gastrointestinal reactions, allergies, and injection site skin reactions (OR = 0.19, 95% CI 0.09–0.41, <i>P</i> &lt; 0.01).</p> Conclusion <p>The findings of this systematic review and meta-analysis suggest that the use of fondaparinux among pregnant women has certain advantages. However, these conclusions warrant further validation through high-quality, large-scale studies conducted in multiple countries. (PROSPERO–CRD42024591579).</p>