BACKGROUND: The Model for End-stage Liver Disease (MELD) has been used as a prognostic tool since 2002 to predict pre-transplant mortality. Increasing proportions of transplant candidates with higher MELD scores, combined with improvements in transplant outcomes, mandate the need to study surgical outcomes in patients with MELD scores of >/=40. METHODS: A retrospective longitudinal analysis of United Network for Organ Sharing (UNOS) data on all liver transplantations performed between February 2002 and June 2011 (n = 33 398) stratified by MELD score (/=40) was conducted. The primary outcomes of interest were short- and longterm graft and patient survival. A Kaplan-Meier product limit method and Cox regression were used. A subanalysis using a futile population was performed to determine futility predictors. RESULTS: Of the 33 398 transplant recipients analysed, 74% scored/=40 at transplantation. Recipients with MELD scores of >/=40 were more likely to be younger (P < 0.001), non-White and to have shorter waitlist times (P < 0.001). Overall patient survival correlated inversely with increasing MELD score; this trend was consistent for both short-term (30 days and 90 days) and longterm (1, 3 and 5 years) graft and patient survival. In multivariate analysis, increasing age, African-American ethnicity, donor obesity and diabetes were negative predictors of survival. Futility predictors included patient age of >60 years, obesity, peri-transplantation intensive care unit hospitalization with ventilation, and multiple comorbidities. CONCLUSIONS: Liver transplantation in recipients with MELD scores of >/=40 offers acceptable longterm survival outcomes. Futility predictors indicate the need for prospective follow-up studies to define the population to gain the highest benefit from this precious resource.