Background & Aims: The treatment of choice for early or moderately advanced hepatocellular carcinoma (HCC) with good liver function remains controversial. We evaluated the therapeutic impacts of surgical resection (SR), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA) on long-term outcomes in patients with HCC. Methods: A database constructed on the basis of a Japanese nationwide survey of 28,510 patients with HCC treated by SR, PEI, or RFA between 2000 and 2005 was used to identify 12,968 patients who had no more than 3 tumors (?3cm) and liver damage of class A or B. The patients were divided into SR (n=5,361), RFA (n=5,548), and PEI groups (n=2,059). Overall survival and time to recurrence were compared among them. Results: Median follow-up was 2.16 years. Overall survival at 3 and 5 years were respectively 85.3%/71.1% in the SR group, 81.0%/61.1% in the RFA, and 78.9%/56.3% in the PEI. Time to recurrence at 3 and 5 years were 43.3%/63.8%, 57.2%/71.7%, and 64.3%/76.9%, respectively. On multivariate analysis, the hazard ratio for death was significantly lower in the SR group than in the RFA (SR vs. RFA:0.84, 95% confidence interval, 0.74-0.95; P=0.006) and the PEI (SR vs. PEI:0.75, 0.64-0.86; P=0.0001). The hazard ratios for recurrence were also lower in the SR group than in the RFA (SR vs. RFA:0.74, 0.68-0.79; P=0.0001) and the PEI (SR vs. PEI:0.59, 0.54-0.65; P=0.0001). Conclusions: Our findings suggest that surgical resection results in longer overall survival and shorter time to recurrence than either RFA or PEI in patients with HCC.