Background and Aims Endoscopic retrograde cholangiopancreatography (ERCP)-guided biliary stent placement is a minimally invasive interventional therapy with demonstrable efficacy for patients with malignant obstructive jaundice (MOJ) who have no chance of radical surgery. However, the risk factors affecting the early bilirubin lowering effect are still unclear yet. Therefore, this study was conducted to analyze the risk factors affecting the therapeutic effect, so as to provide guidance for clinical intervention.Methods The clinical data of MOJ patients with no chance of radical surgery undergoing ERCP-guided biliary stent placement from January 2014 to January 2021 in Department of Hepatobiliary Surgery, Affiliated Hospital of Zunyi Medical University were retrospectively collected. The bilirubin lowering effects on 4-7 d and 1 month after operation were observed. The risk factors affecting the bilirubin lowering effect were determined by univariate analysis and multivariate Logistic regression analysis.Results A total of 171 patients undergoing successful ERCP-guided biliary stent placement were enrolled. Of the 171 patients, the total bilirubin (TBIL) level decreased more than 30% compared with the preoperative value in 100 cases (significant efficacy), and the degree of TBIL decrease did not reach above standard in 61 patients (unsatisfactory efficacy), and the total effective rate was 64.3% (110/171). Among the 63 patients with complete postoperative 1 month follow-up data, the TBIL level returned to normal in 31 cases and did not return to normal in 32 cases, and the total recovery rate was 49.2%. High-grade obstruction (OR=9.223, P<0.01) and preoperative Child-Pugh class C (OR=2.864, P<0.01) were independent risk factors for bilirubin lowering effect on 4-7 d after operation. High-grade obstruction (OR=13.813, P<0.05) and plastic stent implantation (OR=76.981, P<0.01) were independent risk factors for bilirubin lowering effect on 1 month after surgery.Conclusion ERCP-guided biliary stent implantation is an effective way to reduce jaundice in MOJ patients losing the chance of radical surgery. For patients with risk factors affecting bilirubin lowering, the relevant intervention should be undertaken as much as possible and physician-patient communication should be reinforced. As for the stent selection, comprehensive consideration involving many factors is recommended.