Background <p>Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) pose significant threats to patient outcomes, frequently resulting in multiple organ dysfunction syndrome (MODS) and elevated mortality rates. This study investigates MODS outcomes among ALF and ACLF patients in China, identifying key factors that influence mortality and prognosis.</p> Methods <p>A retrospective cohort analysis was conducted at a specialized tertiary hospital in Beijing, covering the period from June 2009 to May 2022, which included 585 patients:195 with ALF and 390 with ACLF.</p> Results <p>Among these, 61% of ALF patients and 45.1% of ACLF patients developed MODS. ALF patients exhibited a higher incidence of organ failures and significantly higher median admission critical illness scores. Multivariate logistic regression analysis identified age, number of organ failures, and platelet count as independent predictors of 90-day mortality. Kaplan-Meier survival hazards analysis revealed significantly higher 90-day cumulative mortality rates for ALF patients compared to ACLF patients (33.8% vs. 25.9%, <i>p</i> = 0.009).</p> Conclusion <p>Approximately 50% of liver failure patients progress to MODS, with ALF patients demonstrating a higher incidence of MODS and poorer 90-day prognoses.</p>