The aim of this study was to evaluate prognostic factors after the recurrence of hepatocellular carcinoma (HCC) in patients who had undergone hepatic resection. We used univariate and multivariate retrospective analyses of 29 clinicopathologic factors in 143 patients with recurrent HCC. Patients were classified into four groups according to the positivity of tumor markers at the time of recurrence. Survival rates and prognostic factors were then compared among the four groups. Multivariate analysis revealed four independent prognostic factors at recurrence: albumin level < 3.5 g/dl ( p = 0.0003), period until recurrence </= 1 year ( p = 0.0004), positive status of alpha-fetoprotein and des-gamma-carboxy prothrombin (AFP+/DCP+) ( p < 0.0001), and portal vein invasion ( p < 0.0001). Among groups with varying status of AFP/DCP, the survival rate in patients with AFP+/DCP+ at recurrence was significantly lower than those in the other three groups (+/+ 15.9% vs. +/- 47.2%, -/+ 44.8%, or -/- 61.1% at 3 years: p < 0.05). The AFP+/DCP+ group also had significantly higher rates of the recurrence appearing </= 1 year after operation (+/+ 68.3% vs. +/- 45.2%, -/+ 41.9%, or -/- 32.5%: p = 0.0108), extrahepatic recurrence (29.3% vs. 6.5%, 9.7%, or 5.0%: p = 0.0026), and no treatment at recurrence (29.3% vs. 9.7%, 9.7%, or 5.0%: p = 0.0115). These results indicate that the tumor markers AFP and DCP are significant prognostic factors for recurrent HCC, and their monitoring is essential for improving the prognosis after recurrence.