Cirrhosis is associated with a procoagulant state that may worsen disease evolution. Anticoagulation could be of particular interest in these patients. However, evidence on the use of DOAC in patients with cirrhosis is limited. Our aim was to explore the in vitro effect of DOAC on thrombin generation (TG) in plasma from patients with cirrhosis compared to healthy controls.Platelet-poor-plasma was obtained from patients with cirrhosis (n=87; Child-Turcotte-Pugh score: A n=68; B n=14; C n=5) and controls (n=17). TG was assessed with ST-Genesia. Plasma from patients with cirrhosis and TM-mediated inhibition of endogenous thrombin potential 50% as "non-procoagulant" (n=20). Plasma samples were spiked with apixaban, edoxaban, rivaroxaban or dabigatran at final concentrations of 50 and 150 ng/ml. TG was measured (DrugScreen) in plasma samples without and with DOAC. Apixaban, edoxaban, and rivaroxaban demonstrated a significantly reduced inhibition of in vitro TG parameters in highly procoagulant plasma from patients with cirrhosis compared to controls, whereas possibly artefactual results were observed with dabigatran.The anticoagulant potency of DOAC differs according to the individual procoagulant potential. Highly procoagulant plasmas from patients with cirrhosis are less sensitive to the anticoagulant action of apixaban, edoxaban, and rivaroxaban compared to control plasmas. These results, if confirmed in vivo, would support the concept of personalizing anticoagulant treatment in patients with a highly procoagulant state.