BACKGROUND AND STUDY AIMS: Biliary stricture after radiofrequency ablation (RFA) for nodules of hepatocellular carcinoma (HCC) close to major bile ducts sometimes causes septic complications and liver failure. Therefore, it may require interventional drainage for decompression during the follow-up period. The purpose of this study is to clarify the feasibility and safety of bile duct cooling using an endoscopic nasobiliary drainage (ENBD) tube in RFA for HCC close to major bile ducts. PATIENTS AND METHODS: Between August 2003 and July 2007, 14 consecutive patients (14 nodules) undergoing RFA with cooling by an ENBD tube for HCCs close to major bile ducts were enrolled in this study. We infused chilled saline solution via the ENBD tube at 1ml/s to prevent heat damage during RFA. As controls, 11 patients (13 nodules) undergoing RFA without cooling close to major bile ducts between April 2001 and August 2003 were reviewed. The major outcomes for evaluation were biliary complications and the secondary outcome was local tumor recurrence. RESULTS: There were no significant differences in tumor recurrence between the two groups. However, the rate of biliary complications was significantly lower in the cooling group than in the non-cooling group (0% vs. 39%, P=0.02). CONCLUSIONS: Cooling of bile ducts via an ENBD tube can prevent biliary complications induced by RFA of HCC close to major bile ducts without increasing local recurrence. This technique increases indication of RFA in difficult cases.