Background: The usefulness of the Total Thrombus-Formation Analysis System ® (T-TAS ® ) for monitoring the anticoagulant effects of non-vitamin K oral anticoagulants (NOACs) in clinical practice has been poorly addressed. Methods: NOACs (rivaroxaban and apixaban) were added to whole blood from healthy subjects in an in vitro study, and their effects on thrombus formation were evaluated by the T-TAS ® . We also evaluated antithrombotic effects using ex vivo samples of whole blood from patients given rivaroxaban or apixaban at the respective trough and peak drug concentrations. Results: T-TAS ® could determine anticoagulant effects in whole blood treated with rivaroxaban or apixaban in vitro . The increases in the anticoagulant effects of rivaroxaban and apixaban from the trough to peak concentrations in whole blood were successfully monitored by the T-TAS ® using ex vivo samples. The antithrombotic effects of rivaroxaban and apixaban (in terms of factor Xa inhibition) at the peak were strongly linked to those at the trough. Conclusion: T-TAS ® could be a clinically useful tool for monitoring the anticoagulant effects of factor Xa inhibitors, and may represent an accurate quantitative analysis. J Clin Med Res. 2016;8(12):899-907 doi: http://dx.doi.org/10.14740/jocmr2773w