Vascular endothelial growth factor (VEGF) is pivotal in the development of hepatocellular carcinoma (HCC). Studies have demonstrated the prognostic value of circulating VEGF levels in patients undergoing liver resection or locoregional therapy (LRT) for HCC. We investigated the significance of preoperative plasma VEGF levels in patients with HCC undergoing liver transplantation (LT) at a Western transplant center. Pre-LT plasma VEGF levels were measured with an enzyme-linked immunoassay for 164 patients with HCC undergoing LT. The preoperative plasma VEGF level was correlated with clinicopathological variables and overall and recurrence-free post-LT survival. A higher pre-LT plasma VEGF level was significantly associated with pre-LT LRT (P=0.01), multiple tumors (P=0.02), a total tumor diameter5 cm (P=0.01), bilobar tumor distribution (P=0.03), tumor vascular invasion (VI; P<0.001), and HCC beyond the Milan criteria (P<0.001). Patients with a plasma VEGF level>44 pg/mL had significantly worse overall and disease-free survival than those with VEGF levels44 pg/mL (P=0.04 and P=0.02, respectively). In a multivariate analysis, a plasma VEGF level>44 pg/mL was independently associated with tumor VI (P<0.001) and recurrence-free survival (hazard ratio=2.12, 95% confidence interval=1.08-4.14, P=0.03). In conclusion, in patients with chronic end-stage liver disease and HCC, a pre-LT plasma VEGF level>44 pg/mL may be a predictor of tumor VI and recurrence-free post-LT survival. Liver Transpl 21:101-111, 2015. (c) 2014 AASLD.