It is well established that there is an increased incidence of gallstones in obese adults and adolescents. In adults, gallstones are more frequent in females than males and this is mirrored in adolescents.In adults, both excess weight and rapid weight loss are associated with gallstone development. In our study, placebo recipients, who generally did not have significant weight reductions from baseline, did not develop gallstones. In contrast, a greater proportion of orlistat-treated participants achieved significantly greater weight loss from baseline and would therefore be at higher risk of developing gallstones. At study end, 6 of the orlistat-treated participants, all girls aged 13 to 15 years with a mean weight loss of 17.6 kg, had asymptomatic cholelithiases identified on ultrasound. Five of these participants developed gallstones during the study and 1 additional participant already had a cholecystectomy prior to study entry. However, the absence of gallstone formation in orlistat-treated participants who had BMI decreases without large weight reductions suggests that gallstone development was related to weight loss and not to the intrinsic effect of orlistat. Indeed, previous studies have shown no increase in the lithogenic index of bile and no evidence of microcrystal formation in the gallbladder with orlistat treatment.There were no cases of acute cholecystitis, although 1 patient who lost approximately 15 kg and was taking oral contraceptives had symptomatic cholelithiasis and a subsequent cholecystectomy.