BACKGROUND In patients with advanced malignant obstructive jaundice (MOJ), it remains an intractable problem to maintain biliary patency, because repeated stent occlusion and poor immune condition can lead to serious infection. The aim of this study was to investigate the effect of endobiliary ablation combined with immune nutrition (IN) on advanced MOJ. MATERIAL AND METHODS A prospective randomized pilot study of patients undergoing percutaneous transhepatic biliary drainage (PTBD) for advanced MOJ was conducted. From January 2018 to December 2020, patients fulfilling eligibility criteria were enrolled and randomized into 2 groups: patients who received only PTBD and standard early enteral nutrition were defined as the control group, and those who underwent additional endobiliary ablation and early IN on basis of the standard therapy were defined as the study group. Primary outcome was assessment of the quality of life based on time to resuming normal daily activities, duration of stent patency, and the overall survival (OS). Secondary outcomes included time before relief of jaundice, hospital stay, inflammation responses, and related complications. RESULTS We included 59 patients: 28 in the study group and 31 in the study group. Baseline characteristics were well balanced between the 2 groups. No statistically significant difference was found in time to resuming normal daily activities between the 2 groups. However, the study group presented statistically longer median duration of stent patency and survival time compared to the control group (stent patency 10.2 months vs 6.8 months, survival 9.6 months vs 7.1 months). The median time for relief of jaundice and the incidence of infection were similar between the 2 groups, but values of inflammatory response markers 3 days after the operation were significantly lower in the study group. No significant difference was found between the 2 groups in overall incidence of complications. CONCLUSIONS For patients at the advanced stage of MOJ, endobiliary ablation combined with postoperative IN therapy can significantly improve the quality of life.