Abstract Context.—Direct thrombin inhibitors (DTIs) and fondaparinux represent a new class of anticoagulants. The effects of DTIs on activated partial thromboplastin time and prothrombin time measurements have been reported previously, but there are limited data on the impact of these anticoagulants on other coagulation tests. Objective.—To determine the effects of fondaparinux and 3 DTIs (argatroban, bivalirudin, and lepirudin) on miscellaneous coagulation tests. Design.—Bivalirudin, lepirudin, argatroban, and fondaparinux were added to pooled normal plasma and tested for fibrinogen, antithrombin (thrombin and Xa substrate methods), plasminogen, protein C (clot and chromogenic methods), protein S, von Willebrand factor, D-dimer, lupus anticoagulant testing (dilute Russell viper venom test [DRVVT] with ratio), and factors II, IX, and X activities. Results.—We found no drug interference on antithrombin, plasminogen, chromogenic protein C, von Willebrand factor, or D-dimer results. All DTIs falsely decreased fibrinogen values, while falsely increasing protein C and protein S levels. All DTIs prolonged the DRVVT, and only argatroban yielded DRVVT ratios less than 1.2. Lepirudin demonstrated no effect on factor II activity, and only argatroban demonstrated decreased factor X activity. All DTI samples demonstrated a linear, dose-dependent, false decrease of factor IX activity. Conclusions.—Using in vitro methods, we demonstrated DTI effects on numerous clot-based assays, but we found no interference with latex agglutination, chromogenic, or platelet aggregation methods. Fondaparinux only affected measurement of protein S activity. Caution must be used when interpreting coagulation test results on patients receiving these drugs.