The objective of this study was to review the incidence, risk factors, methods of diagnosis, and outcome of acute acalculous cholecystitis (AAC) and to identify the sensitivity and limitations of current radiographic modalities used to establish the diagnosis. Our study was a retrospective chart review in a tertiary-care university hospital. Over a 53-month period, 27 cases of AAC (17 males, 10 females; mean age 50 years; mean Acute Physiology and Chronic Health Evaluation II score, 17) were encountered. Of these, 14 (52%) occurred in critically ill patients and 17 (63%) in patients recovering from non-biliary tract operations. AAC occurred in 0.19 per cent of surgical intensive care unit admissions and accounted for 14 per cent (27 of 188) of all cases of acute cholecystitis. Presenting symptoms and laboratory values were nonspecific. Twenty patients had radiographic studies before surgery. Among the various radiological studies used for AAC, morphine cholescintigraphy had the highest sensitivity (9 of 10; 90%), followed by computed tomography (8 of 12; 67%) and ultrasonography (2 of 7; 29%). Ten of the 20 patients had more than one study done preoperatively. All 27 patients had an open cholecystectomy. AAC was associated with a high incidence of gangrene (17 of 27 cases; 63%), perforation (4 of 27; 15%), and abscess (1 of 27; 4%). The mortality rate was 41 per cent (11 of 27). We conclude that AAC is a rare, but potentially lethal, disease occurring in critically ill patients and those recovering from non-biliary tract operations. The clinical presentation is nonspecific, and significant delays in diagnosis result in a high incidence of gangrene, perforation, abscess, and death. To improve outcome, a high index of suspicion with early radiographic evaluation, often employing multiple studies, is necessary. An algorithm for the evaluation of patients for suspected AAC is proposed.