Fondaparinux is a synthetic factor Xa inhibitor based on the active site pentasaccharide of heparin. Based on 5 randomized double-blind trials, fondaparinux became the first synthetic factor Xa inhibitor to be approved for clinical use by the Food and Drug Administration specifically for thromboprophylaxis after orthopedic surgery.1–5 More recently, a number of studies have assessed its efficacy in nonorthopedic surgical and medical patients. Fondaparinux has been shown to be equally as effective and safe as dalteparin in high-risk patients undergoing abdominal surgery.6 In acutely ill medical patients, fondaparinux has daparinux slightly elevated the prothrombin time (PT) by 1 second and activated partial thromboplastin time (aPTT) by 5 to 6 seconds, using a single reagent–instrument combination.20 A recent study examined the effects of fondaparinux and direct thrombin inhibitors on coagulation testing. Using mostly Dade Behring reagents, the study found that fondaparinux affected protein S activity resulting in false elevations of protein S levels even at very low (0.2 g/mL) drug concentrations.21 Fondaparinux did not affect fibrinogen, protein C, antithrombin, plasminogen, von Willebrand factor, D-dimer, or factors II, IX, or X. To further assess the influence of fondaparinux on coagulation testing across a wide variety of reagents being used in the United States, we report the results of a College of Pathologists (CAP) proficiency test survey in which the laboratories were asked to perform PT, aPTT, fibrinogen, antithrombin, factor VIII, thrombin time, and anti– factor Xa assays in samples supplemented with different levels of fondaparinux.