Acute acalculous cholecystitis (AAC) is marked by a very high mortality rate but its relative rarity makes its features obscure to many physicians. This often contributes to a delayed diagnosis. In this study, we review one center's experience, examine the clinical features of the disorder, and describe the progression of pathological events that culminate in AAC. We performed a 10-year retrospective review of cases of AAC reported at our institution between 1988 and 1998. Fifteen cases of AAC were identified from this period, during which 5804 cardiovascular operations were performed. The mortality rate was 46.6%. Multiple organ failure was present in 12 of the 15 cases, and 9 of the patients were over 60 years of age. Prolonged hypotension occurred in 13 patients, and fever in all 15. Nine cases of gangrenous gallbladder occurred. Gram-negative septicemia was present in 12. Visceral arterial hypoperfusion was frequently evident at operation or necropsy. Thirteen patients showed clinical jaundice, a disproportionate elevation of the alkaline phosphatase, or both. Heart failure was found in 9 patients. Open cholecystectomy was most often the definitive intervention. Arterial hypoperfusion of the gut and or sepsis appear central to the pathogenesis of AAC in our series. Gallbladder inflammation and cholestasis result and bacterial invasion of the organ ensues, culminating in AAC, frequently with gangrene. A model of the pathogenesis of AAC is discussed.