Surgeons need to adapt to novel treatments for acute cholecystitis (AC) when surgery isn’t an option.

• Percutaneous cholecystostomy is recommended for patients unfit for lumen-apposing metal stents, aiming to transition to cholecystectomy.
• Endoscopic ultrasound-guided gallbladder drainage is advised for never-surgical candidates if conditions allow monitored anesthesia.

Multidisciplinary protocols are essential, though variability exists in institutional practices. Further research is necessary to validate these emerging techniques.