Eosinophilic cholecystitis (EC) is an infrequent and poorly understood inflammatory condition of the gallbladder. First described in 1949, EC may be defined as an inflammatory condition of the gallbladder in which the inflammatory infiltrate is composed predominately of eosinophils so that their presence clearly overshadows the presence of any other inflammatory cell component. In the few reports that describe EC, it has been described in association with acalculous cholecystitis, with subacute cholecystitis lasting 2 to 3 weeks and with several forms of drug therapy. This retrospective clinicopathologic study reviewed the histopathologic features of 217 consecutive cholecystectomy specimens with special clinical reference to the timing of gallbladder removal after symptoms, previous drug therapy, systemic infection, and the presence of cholelithiasis. Pathologically, 48 of these cases (22.2%) contained eosinophils to some degree. Eosinophilic cholecystitis was diagnosed in 14 (6.4%) of the specimens, and another 14 (6.4%) specimens demonstrated substantial numbers of eosinophils but also had other types of inflammatory cells in abundance, including neutrophils and lymphocytes. Of the eight patients with acalculous cholecystitis, six had substantial eosinophils in their gallbladders, whereas the other two patients had no eosinophils. In this study, EC was more prevalent than in other reported series, and it did not show any association with the timing of gallbladder removal after initial symptoms, drug therapy, or other preexisting medical conditions. Eosinophilic cholecystitis is more common than previously recognized and probably represents a subgroup of patients with a unique or hypersensitivity type of inflammatory response to altered bile. Large numbers of eosinophils in the inflammatory infiltrate occurred three times more commonly in patients with acalculous cholecystitis than in patients with cholelithiasis.