BACKGROUND: Intestinal failure (IF) patients require parenteral nutrition (PN) to avoid malnutrition and death. However, they face complications of recurrent sepsis and liver failure. By the time liver failure is discovered, it is often too late for intervention and prognosis on the waiting list is grim. The Model for End-Stage Liver Disease (MELD) has traditionally been used to predict mortality in patients with liver failure but has never been analyzed in IF patients who are at risk for liver complications. C-reactive protein (CRP) is an acute inflammatory marker that has been shown to reflect disease progression in nonalcoholic steatohepatitis, a disease that in many ways resembles PN-associated liver disease. MELD and CRP are promising clinical markers of disease progression in IF patients on PN. METHODS: The authors performed a retrospective, case-control study to compare levels of MELD and CRP within the entire population of 133 adult patients referred to Northwestern Memorial Hospital for IF from 1999 to 2006. RESULTS: Elevated MELD score is strongly predictive of increased mortality over the subsequent 6 months. Elevated CRP is strongly predictive over a smaller 3-month window. One-year mortality was significantly greater in patients who have either elevated MELD scores or serum CRP levels. CONCLUSIONS: In this study, the authors evaluated for the first time use of MELD and serum CRP as predictive markers of mortality in IF patients. Both seem to be promising clinical tools to identify which patients are at highest risk for complication.