AIM: To investigate the clinicopathological risk factors for immediate post-operative fatal recurrence of hepatocellular carcinoma (HCC), which may have practical implication and contribute to establishing high risk patients for pre- or post-operative preventive measures against HCC recurrence.METHODS: From June 1994 to May 2004, 269 patients who received curative resection for HCC were reviewed.Of these patients, those who demonstrated diffuse intrahepatic or multiple systemic recurrent lesions within 6mo after surgery were investigated (fatal recurrence group). The remaining patients were designated as the control group, and the two groups were compared for clinicopathologic risk factors.RESULTS: Among the 269 patients reviewed, 30patients were enrolled in the fatal recurrence group.Among the latter, 20 patients showed diffuse intrahepatic recurrence type and 10 showed multiple systemic recurrence type. Multivariate analysis between the fatal recurrence group and control group showed that preoperative serum alpha-fetoprotein (AFP) level was greater than 1 000 μg/L (P=0.02; odds ratio= 2.98),tumor size greater than 6.5 cm (P=0.03; OR=2.98),and presence of microvascular invasion (P= 0.01;OR=4.89) were the risk factors in the fatal recurrence group. The 48.1% of the patients who had all the three risk factors and the 22% of those who had two risk factors experienced fatal recurrence within 6 mo after surgery.CONCLUSION: Three distinct risk factors for immediate post-operative fatal recurrence of HCC after curative resection are pre-operative serum AFP level＞1 000 μg/L,tumor size＞6.5 cm, and microvascular invasion. The high risk patients with two or more risk factors should be the candidates for various adjuvant clinical trials.