The surgical indications for multiple hepatocellular carcinomas (HCCs) and for HCC with portal hypertension (PHT) remain controversial. We reviewed 434 patients who had undergone an initial resection for HCC and divided them into a multiple (n = 126) or single (n = 308) group according to the number of tumors. We also classified 386 of the patients into a PHT group (n = 136) and a no-PHT (n = 250) group according to whether they had PHT (defined by the presence of esophageal varices or a platelet count of <100,000/microL in association with splenomegaly). Among Child-Pugh class A patients, the overall survival rates in the multiple group were 58% at 5 years, and 56% in the PHT group, which were lower than those in the single group (68%, P = .035) and the no-PHT group (71%, P = .008). Among Child-Pugh class B patients with multiple HCCs, the 5-year overall survival rate was 19%. Multivariate analyses revealed that the presence of multiple tumors was an independent risk factor for postoperative recurrence (relative risk, 1.64; 95% confidence interval, 1.23-2.18; P = .001). A second resection resulted in satisfactory overall survival after the diagnosis of recurrence in the multiple (73% at 3 years) or PHT (73%) groups, as well as in the single (79%) or no PHT (81%) groups. Resection can provide survival benefits even for patients with multiple tumors in a background of Child-Pugh class A cirrhosis, as well as in those with PHT.