Background: Local recurrence rates after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) vary from 2% to 36% in the literature. Limited data were available about the prognostic significance of local recurrence. Study Design: Between April 2001 and March 2006, 273 patients with 357 hepatocellular carcinoma nodules underwent RFA, with radiologically complete tumor ablation after a single session of RFA. The risk factors of local recurrence and its impact on overall survival of patients were analyzed. Results: With a median followup period of 24 months, local recurrence occurred in 35 patients (12.8%). By multivariate analysis, tumor size > 2.5 cm was the only independent risk factor for local recurrence. There was no notable difference in overall survival between patients with and without local recurrence. By multivariate analysis, local recurrence more than 12 months after RFA and complete response after additional treatment of local recurrence were associated with better overall survival in patients with local recurrence. Conclusions: This study demonstrated that tumor size > 2.5 cm was the main risk factor for local recurrence after RFA of hepatocellular carcinoma. Our data suggested that additional aggressive treatment of local recurrence aimed at complete tumor response improves overall survival of patients. Late local recurrence was also associated with better prognosis, suggesting different tumor biology between early and late local recurrent tumors after RFA.