This study was aimed at investigating whether it is possible, on the basis of the presence of multiple factors, to select a population with a higher prevalence of gallstones than that predicted simply on the basis of age and sex. Thus, we selected and screened for the presence of previously undiagnosed gallstones subjects with at least four of the following variables: female sex, age over 40, obesity, diabetes, biliary colic, family history of gallstones or cholecystectomy, hypertriglyceridemia, parity, and oral contraceptive use. The a priori probability (or expected prevalence) of having previously undiagnosed gallstones was calculated for each subject on the basis of sex and age according to data derived from epidemiological studies performed in Italy in the general population. Among the 821 males and 3930 females participating in this study, previously undiagnosed gallstones (GS) were found in 135 (16.4%) males and 691 (17.6%) females. The ratio between observed and expected prevalence of GS was higher in males (3.09) than in females (2.32). The highest ratios between observed and expected prevalence of GS were found in the lowest classes of expected prevalence in both sexes. The best predictors of the presence of GS were age, biliary colic, and diabetes in males and age, biliary colic, obesity, and number of pregnancies in females. It is concluded that selection of subjects with multiple factors associated with GS increases the a priori probability of GS diagnosis by a factor 2 in females or 3 in males. Stricter selection criteria should be used for females.