Background Acute-on-chronic liver failure (ACLF) is an increasingly recognized entity encompassing an acute deterioration of liver function in patients with cirrhosis, either secondary to superimposed liver injury or due to extrahepatic precipitating factors such as infection culminating in the end-organ dysfunction. Its main features are reversibility and high short-term mortality due to multiorgan failure (MOF). We aimed to analyze the clinical, laboratory, and etiological predictors of mortality and outcome in patients with ACLF. Methods We evaluated 1215 patients with chronic liver disease; 90 patients met the criteria for ACLF. Results The most common cause of underlying chronic liver disease was alcohol, and the most common acute insult (AI) in those patients was superadded alcoholic hepatitis. In all, 50% of all patients died within 30 days (71.1 % within the first 14 days after admission). MOF was the cause of death in 70 % of cases. On multivariate analysis, high serum potassium, serum creatinine higher than 90 mu mol/L, and C-reactive protein > 30 mg/L were found to be independent baseline predictors of mortality. APACHE II (Acute Physiology and Chronic Health Evaluation II) score was the best predictor of short-term mortality (area under the curve (AUC), 0.878). MOF was a valuable predictor of mortality (AUC, 0.923); 33 of 35 patients who had MOF at admission died. Presence of positive systemic inflammatory response syndrome criteria at admission was also correlated with in-hospital mortality (AUC, 0.742). Conclusion ACLF is a serious condition with high short-term mortality. Because ACLF is reversible, it is necessary to identify at-risk patients as soon as possible to treat acute events in a timely manner.