AIM: To investigate the major complications after radiofrequency ablation (RFA) for the treatment of liver tumors and analyze possible risk factors that precipitate these complications.METHODS: From March 2001 to April 2008, 255 patients with liver tumors (205 male, 50 female;age range, 18-89 years; mean age, 56.0 years) who received RFA were enrolled in this study. Of these patients, 212 had hepatocellular carcinoma, 39 had metastatic liver tumors and four had cholangiocellular carcinoma. One hundred and forty eight patients had a single tumor, and 107 had multiple tumors. Maximum diameter of the tumors ranged 1.3-20 cm (mean,5.1 cm). All patients were treated with a cooledtip perfusion electrode attached to a radiofrequency generator (Radionics, Burlington, MA, USA). RFA was performed via the percutaneous approach ( n = 257),laparoscopy ( n = 7), or open surgical treatment ( n = 86). The major complications related to RFA were recorded. The resultant data were analyzed to determine risk factors associated these complications.RESULTS: Among the 255 patients, 425 liver tumors were treated and 350 RFA sessions were performed.Thirty-seven (10%) major complications were observed which included 13 cases of liver failure, 10 cases of hydrothorax requiring drainage, three cases of tumor seeding, one case of upper gastrointestinal bleeding, one case of intrahepatic abscess, one case of bile duct injury, one case of cardiac arrest, and five cases of hyperglycemia. Seven patients had more than two complications. Liver failure was the most severe complication and was associated with the highest mortality. Eleven patients died due to worsening liver decompensation. Child-Pugh classification ( P = 0.001)and choice of approach ( P = 0.045) were related to post-treatment liver failure, whereas patient age,tumor size and number were not significant factors precipitating this complication.CONCLUSION: RFA can be accepted as a relatively safe procedure for the treatment of liver tumors.However, attention should be paid to possible complications even though the incidences of these complications are rare. Careful patient selection and the best approach choice (percutaneous, laparoscopy,or laparotomy) will help to minimize the incidence and morbidity rate of complications which occur after RFA.