427 Background: Official guidelines and retrospective studies have different view on the role of hepatic resection (HR) for patients with large (≥5 cm) multinodular (≥2) hepatocellular carcinoma (HCC) and those involving macrovascular invasion (MVI). We aim to evaluate the efficacy and its variation trend and the safety of HR for these patients in three tertiary care settings. Methods: A consecutive sample of 1,824 patients with Child-Pugh A liver function and large/multinodular HCC or involving MVI and who underwent initial HR were divided into four groups: large/multinodular HCC of the previous (2000-2004, n = 496) and recent five years (2005-2010, n = 765), involving MVI of the previous (n = 242) and recent five years (n = 321). Results: Among our patient sample, the hospital mortality was less than 5% and had a downward trend. Moreover, patients in recent five years have statistically significant longer survival time. Among patients with large/multinodular HCC, patients in recent five years showed a significantly better overall survival than those in previous five years at 1-year (92% vs. 84%), 3-year (69% vs. 61%), and 5-year (45% vs. 40%) (P = 0.004). Moreover, among patients involving MVI, overall survival in recent five years was significantly higher at 1-year (83% vs. 78%), 3-year (50% vs. 41%), and 5-year (25% vs. 17%) (P= 0.033). However, the disease-free survival of recent five years was only slightly higher than that of the previous five years in the two subgroups. Conclusions: HR offers good overall survival for patients with resectable large/multinodular HCC or those involving MVI and with preserved liver function. Outcomes have tended to improve in recent decade.