Gallstones are common in obesity, and in individuals undergoing weight reduction. However, the relationships between body weight, weight reduction, gallbladder bile composition and gallstone formation are not well understood. The present studies were conducted on a cohort of 230 morbidly obese individuals presenting for bariatric surgery. Mean body weight ranged from 90-235.4 kg (mean: 136.2 kg). Body mass index (BMI) ranged from 35.4-94.7 kg/m2. Thirty-two patients (14%) had undergone prior cholecystectomy and 48 (21%) were found to have gallstones by intraoperative ultrasonography. No significant relationship was observed between gallstone prevalence and body weight. Following bariatric surgery weight loss averaged 1.57 kg/week over six months. Absolute weight loss ranged from 13.6-81.3 kg. Symptomatic gallstones requiring cholecystectomy developed in 15/150 patients (10%) over two years of follow-up. In contrast, ultrasonography detected asymptomatic gallstones in 34/92 patients (37%) six months following bariatric surgery. No relationship existed between the amount of weight lost and gallstone formation. Gallbladder bile cholesterol solubility remained constant throughout the entire weight range present in this population. No significant difference in cholesterol solubility was present between persons presenting for bariatric surgery and patients who developed symptomatic gallstones and underwent cholecystectomy following weight reduction. We conclude that gallstones are common in patients with severe obesity both before and following bariatric surgery. However, weight loss per se does not appear to be the major determinant of gallstone formation in persons who weigh in excess of 100 kg.