Background: Since the first description of gas gangrene of an internal organ by Fraenkel in 1889, few cases of acute organ failure following Clostridium perfringens infection have been described in the medical literature. Isolated Clostridium perfringens infection with subsequent sepsis syndrome is an extremely rare clinical syndrome. A consecutive pattern of multiple organ failure generally has a very high mortality rate. Methods: Individual case report and literature review. Results: A 58-year-old male patient developed fulminant necrotic liver failure following a Clostridium perfringens infection. Despite all intensive care measures, including computed tomography-guided drainage, the condition of the patient deteriorated rapidly and the patient died. In this case report we characterize the symptoms of gas gangrene isolated to the liver and compare the treatment measures instituted with the medical literature. Conclusions: In our presented case, primary malignant disease of the papilla of Vater and resection by a Whipple procedure with a hepatico-jejunostomy were a decisive cause of the gas gangrene in the liver. The origin is probably ascension up the common hepatic duct of gut-derived bacteria.