Acute decompensation (AD) of cirrhosis is defined by the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination of these, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF), while their absence defines AD. We designed the PREDICT study, a European, prospective, observational study, to characterize the clinical course of AD and predict ACLF.A total of 1071 patients with AD were enrolled to collect detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed-up for 3 months. The 12-month outcomes (liver transplantation, and death) were also recorded.Three groups of patients were identified: Pre-ACLF patients (n=218), who developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but not developing ACLF and had 21.0% and 35.6% mortality rates. Stable decompensated cirrhosis (SDC) patients (n = 620) who were neither readmitted, nor developed ACLF and showed a 1-year mortality of only 9.5%. The 3 groups differed significantly in the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in the SDC) and prevalence of surrogates of severe portal hypertension throughout the study (high in UDC versus low in pre-ACLF and SDC).Acute decompensation without ACLF is a heterogeneous condition with three different clinical courses and two major pathophysiological mechanisms: systemic inflammation and portal hypertension. Prediction of ACLF development remains a major future task.