Despite the recent advances in hepatobiliary imaging, the diagnosis of chronic acalculous gallbladder disease remains difficult. A retrospective study was undertaken to assess the value of a multiimaging approach in detecting chronic acalculous gallbladder disease and in predicting which patients would obtain symptomatic relief after cholecystectomy. Of 199 patients with chronic cholecystitis, 26 (13%) had no gallstones. Of these 26, only 17 (65%) had symptoms related to chronic cholecystitis; in the remainder, the histologic diagnosis was made incidentally. After cholecystectomy, 13 (76%) of the 17 symptomatic patients obtained long-term symptomatic relief, while in four, the symptoms recurred. Among patients with histologic changes of chronic cholecystitis, biliary scintigraphy was the most sensitive technique (sensitivity, 89%). The sensitivity of sonography and oral cholecystography was 61.5% and 66%, respectively. However, for identifying symptomatic patients who may obtain long-term symptomatic relief after cholecystectomy, the accuracy of sonography, oral cholecystography, and biliary scintigraphy was 82%, 86%, and 38%, respectively. When two tests were in agreement the accuracy was 88%. For chronic acalculous cholecystitis, more than one study must be performed in order to make the correct diagnosis and to predict good results from cholecystectomy.