Severe acute cholangitis is a life-threatening medical emergency. Endoscopic biliary drainage (EBD) or percutaneous transhepatic biliary drainage (PTBD) is usually used for biliary decompression. However, it can be risky to transport a critical patient to the radiology unit. We aimed to compare clinical outcomes between bedside, radiation-free EBD and fluoroscopic-guided PTBD in patients under critical care. Methods: A retrospective study was conducted on critically ill patients admitted to the intensive care unit with biliary obstruction and cholangitis from January 2011 to April 2020. Results: A total of 16 patients receiving EBD and 31 patients receiving PTBD due to severe acute cholangitis were analyzed. In the EBD group, biliary drainage was successfully conducted in 15 (93.8%) patients. Only one patient (6.25%) encountered post-procedure pancreatitis. The 30-day mortality rate was no difference between the 2 groups (32.72% vs. 31.25%, p = 0.96). Based on multivariate analysis, independent prognostic factors for the 30-day mortality were a medical history of malignancy other than pancreatobiliary origin (HR: 5.27, 95% confidence interval [CI]: 1.01–27.57) and emergent dialysis (HR: 7.30, 95% CI: 2.20–24.24). Conclusions: Bedside EBD is safe and as effective as percutaneous drainage in critically ill patients. It provides lower risks in patient transportation but does require experienced endoscopists to perform the procedure.