The objective of this study were to evaluate the efficacy of hepatic resection for large hepatocellular carcinomas (HCCs) and examine clinicopathologic factors influencing overall survival after resection of a large HCC. The pre-, intra-, and postoperative factors and long-term outcome of 26 patients with HCCs >10 cm who underwent hepatic resection (group A) were compared with the those of 143 patients with HCCs < or =10 cm (group B). Hepatic resection for large HCCs can be performed with a mortality rate of 3.8%, which was similar to the rate for group B (2.1%). The overall cumulative survival results for group A (1 year 41.0%, 3 years 29.3%, 5 years 29.3%; median survival 10.1 months) were markedly worse than those for group B (1 year 93.1%, 3 years 74.5%, 5 years 44.7%; median survival 53.4 months) (p < 0.0001). Multivariate analysis identified venous invasion as an independent risk factor of survival of patients with a large HCC. The overall cumulative survival results in patients with venous invasion (1 year 28.0%, 3 years 0%; median survival 6.4 months) were markedly worse than in patients without venous invasion (1 year 64.8%, 3.5 years 64.8%; median survival, 51.8 months) (p < 0.0066). We concluded that hepatic resection can be performed safely for HCCs >10 cm with a low mortality rate. It appears reasonable to believe that hepatic resection is the treatment of choice for large HCCs without venous invasion.