Questions: How may gallstones develop if there is no hemolytic disorder and no malformation or alteration of the gallbladder and cystic ducts? Was there a change in the incidence of stones and the assignment of the patients to different age groups? The literature gives answers to these questions on the basis of only few cases. Therefore, a relatively large prospective database of collected cases during 30 years shall be used to give additional answers. Methods: The data are derived from 111 children with symptomatic gallstones without hemolytic diseases. 109 of them required operative therapy. They were examined preoperatively and postoperatively maximum during 30 years of follow-up as well according to a defined program. This program includes taking the patient’s history, evaluation of clinical, radiological including sonographical examination, exclusion of hemolytic primary diseases, histological investigation of intraoperatively gained specimens of the gallbladder, and the spectroscopic qualitative as well as semiquantitative analysis of stones and bile. Results: (1) The qualitative and quantitative composition of the stones is different in the four age groups. (2) The causes of lithogenesis are different in the four age groups. (3) Children with long-term TPN, after cardiopulmonary bypass operations, after extended small bowel resection, suffering from obesity, and girls using hormonal contraception are at risk of developing gallstones. We recommend to observe these patients by repeated ultrasound controls for gallstone formation during a minimum of 10 years. (4) Malformations and pathological alterations of the gallbladder are rare causes for increased lithogenity. The gallbladder appeared morphologically normal in 61% of patients with symptomatic gallstones. (5) An increased frequency of gallstones during the last 30 years was only observed in the age group under 1 year.