The aim of this study was to examine the effects of NOACs (dabigatran, rivaroxaban, and apixaban) on the thrombin generation assay (TGA) in vivo. We administered healthy volunteers regular doses of NOACs, and measured TGA before and after administration. As a result, rivaroxaban and apixaban, which are direct Xa inhibitors, significantly decreased thrombin generation after administration within four to six hours. With apixaban, thrombin generation was significantly inhibited after administration within 24 hours. Also, with rivaroxaban, although there were milder effects as compared with apixaban, thrombin production was significantly decreased after administration within 24 hours. On the other hand, with dabigatran, which is a direct thrombin inhibitor, a paradoxical effect was seen in the peak and ETP, which are criteria to evaluate TGT after administration. However, a prolonged lag time was observed in each time zone after administration, and similarly to apixaban, such prolongation was also observed 24 hours after the initiation of administration. From these results, it is suggested that TGA is useful for assessing the influence of NOACs on coagulation.