Cumulative recurrence after surgical resection for hepatocellular carcinoma (HCC) is very high. Several retrospective analyses have shown that liver transplantation was more effective than resection for patients with HCC at early tumor stages. Consequently, in January 1990, we decided to prospectively indicate orthotopic liver transplantation (OLT) as the first surgical treatment for small, localized HCC in cirrhotic patients without nodal involvement independently of the degree of liver function. The aim of this prospective cohort study was to analyze prognosis, recurrence rate, and survival after liver transplantation in patients in whom the main indication was HCC with cirrhosis. Thirty-eight patients in whom the main indication for liver transplantation was HCC and hepatic cirrhosis were compared with 136 transplantations because of cirrhosis without tumor, performed in our unit from January 1990 to December 1995. HCC arising in noncirrhotic livers and those incidently discovered after OLT were excluded from the study. Chemoembolization using doxorubicin, lipiodol, and Gelfoam was performed before OLT in 31 patients with good liver function. There were no differences in gender, but HCC patients were older (57 +/- 7 vs. 50 +/- 10 years [P < .001]). Liver function was better in HCC (Child-Pugh score: 6.9 +/- 2 vs. 8.6 +/- 1.8; P < .001), and hepatitis C virus antibody was positive in 31 (82%) vs. 51 (37%) (P < .007). Seven tumors had bilobar involvement (18%). Capsule was present in 22 (58%). The mean size of the tumor was 3.4 +/- 2 cm. Seventeen tumors (45%) were larger than 3 cm, and 4 (11%) were larger than 5 cm. The average number of nodules was 2 +/- 1. The tumor-node-metastasis stage of the tumors was pT1 in 6 patients (16%), 11 were pT2 (29%), 12 were pT3 (31%), and 9 were pT4 (24%). Seven patients were retransplanted in the HCC group (18%) and 19 (14%) in the nontumor group (not significant). Tumor recurrence was detected in three patients (8%). One, 3-, and 5-year survival rates were 82% vs. 79%, 75% vs. 71%, and 63% vs. 68%, respectively, for patients with and without HCC, and no differences were found between the two groups (P = .84). Survival was significantly reduced in patients with a macroscopic vascular invasion and tumors greater than 5 cm in diameter. Recurrence and mortality after liver transplantation in cirrhotic patients with carefully selected HCC are similar to the results in cirrhotic patients without tumor.