Fondaparinux is a parenteral anticoagulant drug and is approved for the prevention of venous thromboembolism in high risk medical patients. A relevant proportion of medical patients have moderate to severe renal insufficiency, which is an independent risk factor for bleeding. This risk may be further increased when low molecular weight heparin or fondaparinux are administered in patients with severe renal insufficiency, defined by a creatinine clearance of lower than 30 mL/min. No clear indications are available to reduce such risk in patients who require thromboprophylaxis. A lower dose of fondaparinux, 1.5 mg daily, has been recently approved for the prevention of venous thromboembolism in the specific population of patients with a creatinine clearance between 20 and 50 mL/min (European Marketing Authorization). However, there are to our knowledge no clinical studies that have assessed the safety and efficacy of this reduced dosage in medical patients.