A 48-year-old female developed acute emphysematous cholecystitis after an endoscopic retrograde cholangiopancreatography (ERCP) for evaluation of sphincter of Oddi dysfunction. Cholecystectomy was performed 2 days later. Cultures grew Clostridium perfringens. The patient received broad-spectrum antibiotics but developed recurrent cholangitic abscesses and intra- and extra-hepatic biliary necrosis. She was managed by percutaneous transhepatic biliary drains. For next 3 years, patient had recurrent episodes of biliary obstruction, cholangitis, and sepsis, resulting in secondary biliary cirrhosis requiring a liver transplantation. Emphysematous cholecystitis is a rare complication of ERCP. Prompt diagnosis and surgical management can prevent further spread of infection to biliary tree.