AIM:To evaluate gallstone incidence and risk factors in a large population-based study.METHODS:Gallstone incidence and risk factors,were evaluated by structured questionnaire and physical examination,respectively,in 9611 of 11 109(86.5%)subjects who were gallstone-free at the cross-sectional study.RESULTS:Six centers throughout Italy enrolled 9611 subjects (5477 males,4134 females,aged 3079 years),9517 of whom were included into analysis:424 subjects (4.4%) had gallstones and 61 (0.6%)had been cholecystectomized yielding a cumulative incidence of 0.67% per year (0.66% in males,0.81% in females).Increasing age,a high body mass index (BMI),a history of diabetes,peptic ulcer and angina,and low cholesterol and high triglyceride levels were identified as risk factors in men while,in females,the only risk factors were increasing age and a high BMI.Increasing age and pain in the right hypocondrium in men and increasing age in females were identified as predictors of gallstones.Pain in the epigastrium/right hypocondrium was the only symptom related to gallstones;furthermore,some characteristics of pain(forcing to rest,not relieved by bowel movements)were significantly associated with gallstones.No correlation was found between gallstone characteristics and clinical manifestations,while increasing age in men and increasing age and BMI in females were predictors of pain.CONCLUSION:Increasing age and BMI represent true risk factors for gallstone disease (GD);pain in the right hypocondrium and/or epigastrium is confirmed as the only symptom related to gallstones.