Obesity is a rather documented risk factor for the formation of gallstones (GS) in women. The magnitude of the increased risk and the rates of GS occurrence, however, have not been well quantified, except for two studies on the risk of symptomatic stones in obese women. We analyzed the incidence of GS in 157 moderately obese women (body mass index, 31.4 +/- 3.6 kg/ m2) followed up prospectively by ultrasound for 2-6 yr (mean 3.95 yr). Women with morbid obesity (body mass index > 40 kg/m2) were excluded from the study, as well as patients having diseases with lithogenic risk. All the enrolled women had normal cholecystosonogram results at the beginning of the study. Age, family history of GS or obesity, parity, age of obesity onset, hyperlipoproteinemia type, plasma cholesterol (total, HDL, LDL), and triglycerides were assessed. The Student's t, the Mann-Whitney rank sum and the Fisher's exact tests were used, as well as the multiple logistic regression for the multivariate analysis. During the survey, 16 of 157 women (10.2%) developed GS. GS were asymptomatic in 11 persons (68.8%). The cumulative incidence of both asymptomatic and symptomatic GS was 2.6 cases/100 obese women.year. During the follow-up, most of the detected GS were asymptomatic, and this explains the higher GS incidence rate found compared with that previously calculated for symptomatic GS. The following risk factors were associated with GS formation: age (p = 0.002), family history of GS (p = 0.011), early obesity onset (p = 0.003), and hyperlipoproteinemia type IV (p = 0.011). A high risk class might be thus identified among obese women, offering a more realistic approach for the primary prophylaxis of GS.