Background Acute-on-chronic liver failure (ACLF) is characterized by the development of a syndrome associated with a high risk of short-term death in patients with acute decompensated cirrhosis, and better biomarkers are needed to predict such outcomes. Sarcopenia, a common complication of cirrhosis, is tightly associated with poor prognosis and increased mortality. In this study, the skeletal muscle index of ACLF patients was measured to determine whether sarcopenia combined with clinical parameters helps in identifying those at high risk of progression. Methods A total of 314 hospitalized ACLF patients were included and allocated into groups of transplantation-free survival (n = 214) or progression (n = 100) within 90 days. Muscle mass was assessed based on the skeletal muscle index. The optimal cutoff value of the AMPAS1 model (age, MELD score, platelet count, alpha-fetoprotein level, sarcopenia and more than one complication combination) for progressive prediction was identified using receiver operating characteristic (ROC) analysis. Results Sarcopenia was an independent risk factor for progression in the ACLF population (HR 3.705 95%CI 2.131-6.441, P