We prospectively investigated the association between a change of serum vascular endothelial growth factor (VEGF) level after transcatheter arterial chemoembolization (TACE) and hepatocellular carcinoma (HCC) patient prognosis. The study involved 147 patients with unresectable HCC treated at the National Cancer Center, Korea, between July and December 2005. Serum samples were collected from each patient before TACE, and 1-2 days and 1 month after TACE. Serum VEGF concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). The log(e)(VEGF/platelets) increased transiently 1-2 days after TACE and declined thereafter. Frequency of previous TACE did not correlate with log(e)(VEGF/platelets). This study found that log(e)(VEGF/platelets) 1-2 days after TACE, but not log(e)(VEGF/platelets) at baseline, was strongly correlated with vascular or nodal invasion and AJCC (American Joint Committee on Cancer)/UICC (International Union Against Cancer) stage, and was significantly greater in men. Relative changes in serum VEGF/platelet levels 1-2 days after TACE (DeltaVEGF) > 0.5 were directly correlated with tumor size, vascular invasion and modified UICC and AJCC/UICC stage (P < 0.05 for each). Additionally, DeltaVEGF > 0.5 was significantly correlated with newly developed extrahepatic metastases one and six months after TACE (P = 0.005 and 0.003, respectively). Progression free survival of patients with DeltaVEGF > 0.5 was significantly worse (P < 0.001) and DeltaVEGF > 0.5 was an independent prognostic factor for PFS (hazard ratio, 3.111; P < 0.001). This study showed that a high increment in serum VEGF level 1-2 days after TACE in HCC patients was associated with distant metastasis and unfavorable outcomes.