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We evaluated the Chronic Liver Failure–Sequential Organ Failure Assessment (CLIF-SOFA) score to predict survival in a Canadian critically ill cohort with acute-on-chronic liver failure.We retrospectively examined 274 acute-on-chronic liver failure patients admitted to a quaternary level intensive care unit (ICU) between April 1, 2000, and April 30, 2011. We evaluated severity of illness scores, including the Acute Physiology and Chronic Health Evaluation (APACHE) II, model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP), SOFA, and CLIF-SOFA.On ICU admission, patients had the following median (interquartile range): APACHE II, 23 (19-28); MELD, 26 (19-35); CTP, 12 (10-13); SOFA, 15 (11-18); and CLIF-SOFA, 17 (13-21). In-hospital survival was 40%. There were no significant differences in survival for cirrhosis etiology, reason, or year of admission. The CLIF-SOFA score had the greatest area under receiver operating curve of 0.865 (95% confidence interval, 0.820-0.909) and outperformed the CTP, MELD, SOFA, and APACHE II scores. Sequential Organ Failure Assessment score performance improved on the third day of ICU admission (area under receiver operating curve, 0.935; 95% confidence interval, 0.895-0.975).The CLIF-SOFA and SOFA scores during the first 3 days of ICU admission appear to be highly predictive of in-hospital mortality.