Radiofrequency ablation (RFA) was introduced recently as a therapeutic modality for hepatocellular carcinoma (HCC), an alternative to percutaneous ethanol injection therapy (PEIT), which is coming into use worldwide. Previously reported treatment efficacy and complication rates have varied considerably. Between February 1999 and February 2003, the authors performed 1000 treatments of RFA to 2140 HCC nodules in 664 patients with a cooled-tip electrode at the University of Tokyo Hospital (Tokyo, Japan). Short-term and long-term complications were analyzed by treatment and session basis. Cumulative survival was also assessed in 319 patients who received RFA as primary treatment (naive patients) and 345 patients who received RFA for recurrent tumor after previous treatment including resection, PEIT, microwave coagulation therapy, and transarterial embolization (nonnaive patients). A total of 40 major complications (4.0% per treatment, 1.9% per session) and 17 minor complications (1.7% per treatment, 0.82% per session) were observed during the observation period until March 31, 2004. There were no treatment-related deaths. Surgical intervention was required in one case each of bile peritonitis and duodenal perforation. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 94.7%, 86.1%, 77.7%, 67.4%, and 54.3% for naive patients, whereas the cumulative survival rates were 91.8%, 75.6%, 62.4%, 53.7%, and 38.2% for nonnaive patients, respectively. The authors confirmed the safety and efficacy of RFA for HCC in a large-scale series and long-term prognosis was satisfactory.