Abstract Background Routine drug monitoring is not required for the two novel direct factor Xa inhibitors apixaban and rivaroxaban. Rapidly available test results might be beneficial in case of bleeding or prior to urgent surgery. Objectives The aim of this study was to evaluate the applicability of the two rotational thrombelastometry (ROTEM®) -modifications Low–tissue factor activated ROTEM® (LowTF–ROTEM®) and Prothrombinase induced clotting time – activated ROTEM® (PiCT®–ROTEM®) for determination of apixaban and rivaroxaban in vitro and ex vivo. Methods Blood samples from 20 volunteers were spiked with apixaban / rivaroxaban to yield samples with ascending drug concentrations ranging from 50 – 400ng/mL. LowTF – and PiCT® modified ROTEM® tests and determination of the corresponding antifactor Xa activity were performed in duplicate in 280 samples. LowTF–ROTEM® tests were performed in samples from 20 patients on apixaban or rivaroxaban therapy and 20 controls. Results There was a strong correlation between apixaban / rivaroxaban plasma concentrations and the LowTF–ROTEM® parameters Clotting time (CT; spearman correlation coefficient (SCC) 0.81 and 0.81, respectively) and Time to maximum velocity (t,MaxVel; SCC: 0.81 and 0.80, resp.) and a low to moderate correlation for the PiCT®–ROTEM® parameters CT (SCC: 0.38 and 0.59, resp.) and t,MaxVel. (0.51 and 0.69, resp.) in the in vitro experiments. LowTF–ROTEM CT was significantly prolonged in patients on apxiaban or rivaroxaban therapy compared to controls. Conclusions LowTF–ROTEM® could be a valuable diagnostic tool for rapid determination of the effect of apixaban and rivaroxaban at the point of care.