The role played by coagulation defects in the occurrence of bleeding in cirrh osis is still unclear. This is partly due to the lack of tests that truly reflec t the balance of procoagulant and anticoagulant factors in vivo. Conventional co agulation tests such as prothrombin time and activated partial thromboplastin ti me are inadequate to explore the physiological mechanism regulating thrombin, be cause they do not allow full activation of the main anticoagulant factor, protei n C, whose levels are considerably reduced in cirrhosis. We used a thrombin gene ration test to investigate the coagulation function in patients with cirrhosis. Thrombin generation measured without thrombomodulin was impaired, which is consi stent with the reduced levels of procoagulant factors typically found in cirrhos is. However, when the test was modified by adding thrombomodulin (i.e., the prot ein C activator operating in vivo), patients generated as much thrombin as contr ols. Hence, the reduction of procoagulant factors in patients with cirrhosis is compensated by the reduction of anticoagulant factors, thus leaving the coagulat ion balance unaltered. These findings help clarify the pathophysiology of hemost asis in cirrhosis, suggesting that bleeding is mainly due to the presence of hem odynamic alterations and that conventional coagulation tests are unlikely to ref lect the coagulation status of these patients. In conclusion, generation of thro mbin is normal in cirrhosis. For a clinical validation of these findings, a pros pective clinical trial is warranted where the results of thrombin generation in the presence of thrombomodulin are related to the occurrence of bleeding. The role played by coagulation defects in the occurrence of bleeding in cirrhosis is still unclear. This is partly due to the lack of tests that truly reflec t the balance of procoagulant and anticoagulant factors in vivo. Conventional co agulation tests such as prothrombin time and activated partial thromboplastin ti me are inadequate to explore the physiological mechanism regulating thrombin, be cause they do not allow full activation of the main anticoagulant factor, protei n C, whose levels are significantly reduced in cirrhosis. We used a thrombin gene ration test to investigate the coagulation function in patients with cirrhosis. Where, when the test was modified by adding thrombomodulin (ie, the prot ein C activator operating in vivo), patients generated as much thrombin as controls. Therefore, the reduction of pro coagulant factors in patients with cirrhosis is compensated by the reduction of anticoagulant factors, thus leaving the coagulat ion balance unaltered. These findings help clarify the pathophysiology of hemost asis in cirrhosis, suggesting that bleeding is mainly due to the presence of hemodynamic alterations and that conventional coagulation tests are unlikely to ref lect the coagulation status of these patients. In conclusion, generation of thro mbin is normal in cirrhosis. For a clinical validation of these findings, a pros pective clinical trial is warranted where the results of thrombin generation in the presence of thrombomodulin are related to the occurrence of bleeding.