Background and aims Acute-on-chronic liver failure (ACLF) is associated with a high mortality rate in the absence of liver transplantation. There is limited data on predictors of survival in ACLF in children. Therefore, we prospectively studied the predictors of outcome of ACLF in children. Methods A prospective evaluation of 31 children in the age group of 1-16 years who fulfilled the criteria for ACLF according to Asian Pacific Association for the Study of the Liver (APASL) 2008 consensus was done. All consecutive children were evaluated for etiology, diagnosis and severity of ACLF. For grading of organ dysfunction, the sequential organ failure assessment (SOFA) score was calculated. SOFA constitutes the parameters of respiration, coagulation, cardiovascular system, central nervous system, and renal and liver functions. We evaluated possible correlation between outcomes and different variables. Results Of the 31 children who fulfilled the criteria for ACLF, the common underlying chronic liver diseases (CLD) were autoimmune hepatitis (AIH) in 41.9% and Wilson disease in 41.9% of the patients. Superinfection with hepatitis A virus (HAV) (41.9%) was the most common etiology of acute deterioration. To find the best predictor for outcome, linear regression analysis was performed. Multivariate analysis revealed that the SOFA score and the International Normalized Ratio (INR) were predictors of survival. Six (19.4%) patients died. Causes of death were multiorgan failure in four and liver failure in two patients. Conclusion The mortality in ACLF is 19.4% and the causes of death were multiorgan failure and liver failure. The SOFA score and INR were predictors of outcome of ACLF in children.