We present the results of a population-based survey carried out in a low income area of Mexico City. The aim of this study is to characterize the prevalence of clinically significant gallbladder disease (CSGD) using the self-reported history of cholecystectomy (CG) or cholelithiasis (CL) demonstrated by cholecystography and/or ultrasonography. The population of the studied area was 15,532 inhabitants, of whom 3505 (22.6%) were age eligible (35-64 year-old men and non-pregnant women). Home interviews were obtained in 2810 (80.2%). A physical and laboratory examination was performed in 2282 individuals (65.1%; 941 men and 1341 women). The prevalence of CSGD in men was 2.0% (95% confidence intervals 1.1-2.9%) and 9.2% in women (95% confidence intervals 7.7-10.7%). Patients with CSGD were older, men (p < 0.003) and women (p < 0.001). Women with CSGD had higher waist to hip circumference ratio (p < 0.06), higher fasting glucose (p < 0.03) as well as 2 h post challenge glycemia (p < 0.04) and insulinemia (p < 0.03). In the multiple logistic regression model only age (p < 0.001) and sex (p < 0.001) remained significantly associated. We conclude that CSGD is quite prevalent in this population. It is associated with age in both genders and in women, higher glucose and insulin levels. The prospective follow-up of this cohort is important since it could generate the information needed to implement a preventive program to diminish the impact of this condition.