A positive association between body mass index (BMI) and risk of esophageal adenocarcinoma has been reported. Barrett esophagus (BE) is a precursor lesion for esophageal adenocarcinoma. Cardiac mucosa (CM) and BE are both reflux-induced metaplastic columnar epithelia in the esophagus. We investigated the association between BMI and BE/CM in a case-control study. A total of 174 BE patients, 333 CM patients, and 274 controls were included in this study. Multivariate logistic regression methods were used to estimate odds ratios (OR) for BE or CM associated with BMI. Linear regression analysis was employed to examine the relationship between length of columnar lined esophagus (CLE) and BMI. A dose-dependent relationship was found between BMI and BE (P=.0004). The multivariate-adjusted OR for BE was 3.3 (95% confidence interval [CI], 1.6-6.7) when obese individuals (BMI >or=30 kg/m(2)) were compared to lean individuals (BMI < 22 kg/m(2)). Similarly, a dose-dependent relationship was found between BMI and CM (P=.03). The multivariate-adjusted OR for CM comparing obese to lean persons was 1.8 (95% CI, 1.04-3.10). The length of CLE was positively related to BMI (P=.04). In conclusion, BMI is associated with BE and CM and appears to act early in the sequence of events leading from gastroesophageal reflux disease to metaplasia (CM and BE) to dysplasia and finally to adenocarcinoma.