To compare the efficacy of hepatic resection (HR) in patients with Barcelona Clinical Liver Cancer (BCLC) Stage B hepatocellular carcinoma (HCC) and examine how that efficacy has changed over time in a large medical center. A consecutive sample of 918 patients with preserved liver function and large and/or multinodular HCC who were treated by initial HR were divided into three groups: those with a single tumor ≥5 cm in diameter ( =582), 2-3 tumors with a maximum diameter>3 cm ( =223), or>3 tumors of any diameter ( =113). Hospital mortality and overall survival (OS) in each group were compared for the years 2001-2007 and 2008-2013. Patients with >3 tumors showed the highest incidence of hospital mortality of all groups ( <0.05). Kaplan-Meier survival analysis showed that OS varied across the three groups as follows: single tumor>2-3 tumors >3+ tumors (all <0.05). OS rate at 5 years ranged from 24% to 41% in all three groups for the period 2001-2007, and from 35% to 46% for the period 2008-2013. OS was signific