To compare the outcomes between anterior versus conventional approach right hepatectomy for large hepatocellular carcinoma (HCC). A total of 188 consecutive patients with large HCC ( > or =5 cm) undergoing right hepatectomy were reviewed retrospectively. Among them, 92 patients received anterior approach right hepatectomy (anterior group) while the other conventional right hepatectomy (conventional group). Their clinicopathologic data and survivals were compared. There were five surgical deaths (2.7%), two in the anterior group and three in the conventional group. The biochemical and tumor pathological data (except for tumor size) of these two groups were comparable. The mean intraoperative blood loss, the number of patients with massive hemorrhage ( >3000 ml) and the volume of blood transfusion of the anterior group were markedly less than those of conventional group. The 1-, 3-year disease-free survival rates of the anterior group were significantly better than those of the conventional group (56.2%, 30.9% vs. 39.1%, 13.0%, P = 0.043). The 1- & 3-year cumulative survival rates of the anterior group were also markedly higher than those of conventional group. The Cox regression model indicated that tumor size [P = 0.014, odd ratio (OD) = 1.074] and surgical procedure (P = 0.009, OD = 0. 468) were independent risk factors correlated with disease-free survival. And the surgical procedure (P = 0.003, OD = 0.369) was the only independent risk factor for postoperative cumulative survival. Anterior approach right hepatectomy can significantly decrease intraoperative blood loss. The postoperative survivals of large HCC patients are significantly improved by anterior approach right hepatectomy.