Background: Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) extending to the main trunk of the portal vein have been considered to be a contraindication to surgical intervention, because tumor cells might be spreading to the opposite lobe of the liver at the time of hepatectomy, and the prognosis of HCC with severe portal invasion is known to be poor. The aim of this study is evaluate the efficacy of hepatectomy and tumor thrombectomy for HCC with tumor thrombus extending to the main portal vein trunk.Methods: Among 979 patients who consecutively underwent primary hepatectomy for HCC in National Cancer Center Hospital, Tokyo, Japan, from 1992 to 2008, forty-five patients with PVTT extending to the first portal branch and main portal vein trunk were evaluated retrospectively. According to the classification the Liver cancer Study Group of Japan, tumor thrombus in first order portal branches, and the main portal vein trunk or the opposite-side portal vein branch were defined as Vp3 and Vp4, respectively. Clinicopathologic data and surgical outcomes between HCC with Vp3 (n=26) and with Vp4 (n=19) were compared.Results: The 1, 3 and 5 year survival rates in all the patients (n=45) were 69.8%, 36.6% and 19.0%, respectively, with a median survival time of 20 months. In the univariate analysis, the indicators of an unfavorable prognosis included tumor size (p=0.0060), alpha-fetoprotein (p=0.0057), surgical margin (p=0.0198), serosal invasion (p=0.00166), residual tumor (p=0.0245), and intrahepatic metastasis (p=0.0026) to be significant prognostic factors. Multivariate analysis revealed serosal invasion (p=0.005) and intrahepatic metastasis (p=0.002) to be significant prognostic factors. There were longer operative time (p=0.0034) and a larger amount of intraoperative bleeding (p=0.0041) in patients with Vp4, but no significant difference in mortality, morbidity and survival between patients with Vp3 and Vp4. Conclusion: A favorable prognosis might be expected even in patients with Vp3 and Vp4, without intrahepatic metastases and serosal invasion. Hepatectomy and thrombectomy for patients with Vp4 seemed to be a safe and effective surgical treatment in the selected patients, because there was no significant difference in mortality, morbidity and survival between patients with Vp3 and Vp4.