To establish diagnostic criteria for acute-on-chronic liver failure (ACLF) in Japan, the Intractable Hepato-Biliary Disease Study Group of Japan performed a multicenter pilot survey for patients fulfilling the APASL, EASL-Clif Consortium, or Chinese Medical Association (CMA) diagnostic criteria for ACLF and found that the APASL criteria were suitable for screening Japanese patients with ACLF when patients whose conditions were triggered by gastrointestinal bleeding were included within the disease entity, while the EASL-Clif Consortium criteria were useful for classifying the severity of the patients' conditions. Based on these observations, the Study Group proposed the following diagnostic criteria for ACLF in Japan: patients with cirrhosis and a Child-Pugh score of 5-9 should be diagnosed as having ACLF when a deterioration of liver function (serum bilirubin level of 5.0 mg/dL or more and prothrombin time value of 40% or less of the standardized values and/or international normalization rates [INRs] of 1.5 or more) caused by severe liver damage develops within 28 days after acute insults, such as alcohol abuse, bacterial infection, gastrointestinal bleeding, or the exacerbation of underlying liver diseases. The severities of the patients can be classified into 4 grades depending on the extent of the deterioration in organ functions, including kidney, cerebral, blood coagulation, circulatory and respiratory functions as well as liver function. The usefulness of these novel criteria should be validated prospectively in a largescale cohort in the future.