A prospective study was carried out to investigate the value of preoperative ultrasound findings for predicting difficulties encountered during laparoscopic cholecystectomy (LC). Altogether 160 consecutive patients with symptomatic gallbladder (GB) disease (130 females, 30 males) referred to the Jordan University Hospital were recruited for the purpose of this study. All patients underwent detailed ultrasound examination 24 hours prior to LC. The overall difficulty score (ODS), as a dependent variable, was based on the following operative parameters: duration of surgery, bleeding, dissection of Calot’s triangle, dissection of gallbladder wall, adhesions, spillage of bile, spillage of stone, and difficulty of gallbladder extraction. Multiple regression analysis was used to assess the significance of the following preoperative ultrasound variables (independent) for predicting the variation in the ODS: size of the GB, number of GB stones, size of stones, location of GB stones, thickness of GB wall, common bile duct (CBD) diameter, and liver size. Only thickness of GB wall and CBD diameter were found to be significant predictors of the variation in the ODS (adjusted R2 = 0.25). We conclude that the preoperative ultrasound examination is of value for predicting difficulties encountered during LC, but it is not the sole predictor.