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Background: Cholangitis after endoscopic retrograde cholangiopancreatography (ERCP) is a major problem for patients with hilar biliary obstruction. To date, it remains unclear whether air-contrast cholangiography (ACC) can reduce cholangitis in these patients. For this reason, our study assesses the efficacy of reducing cholangitis through ACC., Methods: This paper presents a retrospective study conducted at a tertiary university hospital. We enrolled patients who were diagnosed with hilar structures and underwent ERCP between January 2012 and December 2018. From 2015 onwards, ACC was performed following the successful selective cannulation into the dilated intrahepatic bile duct of these patients. The primary aim was to assess patients with cholangitis in both an ACC group and iodine contrast cholangiography (ICC) group., Results: This study included 80 patients, 35 of whom received ACC and 45 who received ICC. There were no differences between the 2 groups in terms of the number of patients who underwent endoscopic papillotomy, endoscopic nasobiliary drainage, endoscopic biliary stent placement, or other technical procedures or complications. A total of 19 patients (23.8%) presented with fever (cholangitis) after the ERCP procedure (4 ACC, 15 ICC; 11.4% vs. 33.3%, respectively; P=0.03). One patient in the ICC group who obtained a plastic stent for palliative drainage died 2 weeks post-ERCP. Among the other 18 cholangitis patients, 8 (1 ACC, 7 ICC) were treated with additional ERCP or percutaneous transhepatic biliary drainage (PTBD), while the remaining 10 only received antibiotics. One patient in the ICC group who obtained a plastic stent for palliative drainage died 2 weeks post-ERCP., Conclusions: We found that ACC significantly reduced the incidence of cholangitis in patients with hilar obstruction., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-462). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)