Hepatic resection is still considered the treatment of choice for hepatocellular carcinoma in patients with liver cirrhosis. Radiofrequency ablation is a new emerging modality. The aim of this study was to compare two homogeneous groups of patients who underwent either surgical resection or laparoscopic radiofrequency, analyzing the factors predicting survival and intrahepatic recurrences with use of a multivariate analysis. From February 1997 to April 2003, 98 patients were enrolled in this prospective study. Inclusion criteria were a single nodule of less than 5 cm, Child A-B class of liver function, and no previous treatment: 40 patients were in the surgical group and 58 patients were in the radiofrequency group. The two groups were homogeneous as far as preoperative characteristics were concerned. Operative mortality was zero, and the rates of operative morbidity were similar. Actuarial survival at 4 years was not significantly different (61% after resection and 45% after radiofrequency). There was a significant higher incidence of intrahepatic recurrences after radiofrequency than after resection (53% versus 30%; P=0.018). This was mainly due to local recurrences, whereas those appearing in other liver segments were similar in both groups. A multivariate analysis showed that the significant factors predictive of an intrahepatic recurrence were the level of alpha-fetoprotein, the etiology of cirrhosis, and the type of the treatment. On the other hand, multivariate analysis of the survival showed that only the level of alpha-fetoprotein was an independent predictor of survival. The results of our study showed a significant lower incidence of intrahepatic recurrences after resection compared with after radiofrequency. This seems not to significantly influence the overall survival, probably because of a prompt and effective treatment of the recurrences themselves.