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Introduction: While the Tokyo Guidelines 2018 suggest primary stone removal for mild to moderate cholangitis, a guideline for severe acute cholangitis is not mentioned. We, therefore, investigated the clinical outcomes of patients with severe acute cholangitis to confirm the usefulness and safety of primary stone removal. Method: This study included 104 severe acute cholangitis patients without gallstone pancreatitis diagnosed at our institution between January 2014 and December 2020. Patients with percutaneous transhepatic biliary drainage as the primary drainage, bile duct stenosis, and endoscopically unidentified bile duct stones were excluded from this study. The clinical results of 14 patients with primary stone removal (primary group) and 23 patients with elective stone removal (elective group) were then retrospectively examined (excluding abnormal values due to underlying diseases). Results: Upon comparing the patient characteristics between groups, the elective group had significantly higher cardiovascular dysfunction (57% vs 7%; p = 0.004), septic shock (39% vs 0%; p = 0.006), disseminated intravascular coagulation treatment (57% vs 14%; p = 0.016), and positive blood cultures (91% vs 43%; p = 0.006) than those in the primary group. Endoscopic sphincterotomy for naïve papilla (90% vs 21%; p = 0.01) and endoscopic nasobiliary drainage (50% vs 9%; p = 0.014) were higher in the primary group, while endoscopic biliary stenting (7% vs 87%; p Discussion: There were no significant differences in adverse events or complete stone removal rates between the two groups. In the primary group, the period from the first endoscopic retrograde cholangiopancreatography to stone removal (0 days vs 12 days; p Conclusion: If patients are appropriately selected, bile duct stones may be safely removed for the treatment of severe acute cholangitis.