Background: Venous thromboembolism (VTE), are few of the most serious complications in ICU. There are Pharmacological and mechanical prophylaxis methods are used to reduce the risk of thromboembolism and the most efficient is the pharmacological methods which is based on a fine balance between their efficacy and the adverse effects associated with them. Objectives: To evaluate, effectiveness, and clinical impact of VTE prophylaxis with fondaparinux and enoxaparin on patient outcomes in different clinical practices. Study design: Meta-analysis was used to address this concern. Sittings: Meta-analysis-based study following the PRISMA (Preferred Reporting Items for Systematic Reviews and MetaAnalyses) guidelines. Methods: Online databases (PubMed/Medline, EMBASE, and Cochrane library) were used for randomized studies which compared differences in clinical outcomes observed with the use of Fondaparinux and enoxaparin in patients who were treated for thromboembolism. Results: Thirteen studies were identified for inclusion in this study, involving a total of 64,350 patients. The risk of bias was low. Meta-analysis found that Fondaparinux result in significant reduction in incidence of bleeding than Enoxaparin (R.R.=0.85 [0.81, 0.88]; 95% CI; I 2=100%; P