Pancreatobiliary disorder is a challenging clinical condition, especially when this condition is causing severe infection or biliary sepsis, and sometimes it requires intensive care unit (ICU) treatment. Biliary drainage is the mainstay of therapy; however, the choice of the drainage method is dependent on the patient's clinical condition and the disease itself. A 79-year-old female was transferred on a ventilator to our ICU from another hospital due to biliary sepsis, a large common bile duct stone, and an infected pancreatic pseudocyst. The patient also has other comorbidities such as heart problems, hypothyroidism, and diabetes mellitus. Bedside percutaneous transhepatic biliary drainage without fluoroscopy and percutaneous cyst aspiration was successfully performed, which improved the patient's condition; this was followed by an endoscopic approach, i.e., endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided pancreatic pseudocyst drainage. The clinical improvement showed itself in the change of the patient's respiratory status and ventilator mode. In conclusion, the percutaneous approach has a big role in managing critically ill patients in the ICU setting. However, expertise, training experience, and a multidisciplinary team approach are very important for successful management and patient outcome. © 2021 The Author(s). Published by S. Karger AG, Basel.