There is increasing evidence that a relevant number of patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria may benefit from liver transplantation (LT). We retrospectively analyzed the prognostic significance of [18F]fludeoxyglucose ([18F]FDG) positron emission tomography (PET) for identifying appropriate LT candidates with advanced HCC on clinical staging. Between 1995 and 2008, 111 patients with HCC were listed for LT. All underwent a pretransplant PET evaluation. LT was performed for 91 of these patients. The tumor recurrence rate after LT was 3.6% for patients with non–[18F]FDG-avid (PET−) tumors, but it was 54.3% for patients with [18F]FDG-avid (PET+) tumors (P < 0.001). The 5-year recurrence-free survival rates were comparable for patients with tumors meeting the Milan criteria (86.2%) and patients with PET− HCC exceeding the Milan criteria (81%) at LT, but these rates were significantly higher than the rate for liver recipients with [18F]FDG-avid advanced HCC (21%, P = 0.002). In a multivariate analysis, negative PET findings (odds ratio = 21.6, P < 0.001), an alpha-fetoprotein level <400 IU/mL (odds ratio = 3.3, P = 0.013), and a total tumor diameter <10 cm (odds ratio = 3.0, P = 0.022) were identified as pretransplant prognostic variables for recurrence-free survival. A PET+ status was assessed as the only independent clinical predictor of tumor-related patient dropout from the waiting list (hazard ratio = 5.7, P = 0.01). Patients with non–[18F]FDG-avid HCC beyond the Milan criteria according to clinical staging may achieve excellent long-term recurrence-free survival after LT. Liver Transpl 18:53–61, 2012. © 2011 AASLD.