BACKGROUND: The incidence of esophageal adenocarcinoma has increased markedly in recent decades in many countries. Obesity is a potential risk factor, although the results of individual studies differ. We did a systematic review and statistical synthesis of studies that evaluated the association between body mass index (BMI) and the risk of esophageal adenocarcinoma or the adjacent gastric cardia adenocarcinoma. METHODS: We identified potential studies using Medline, the Web of Science database, a manual review of the literature and expert bibliographies. Studies were included if they reported (a) a measure of body mass; (b) the occurrence of esophageal or cardia adenocarcinoma diagnosis; and (c) a relative risk or odds ratio (OR) with confidence intervals (CI) or provided sufficient data to permit their calculation. RESULTS: We identified 14 studies (2 cohort, 12 case-control; 2,488 esophageal and 2,509 cardia adenocarcinomas). A high BMI (>25) was associated with an increased risk of esophageal adenocarcinoma (males, OR, 2.2; 95% CI, 1.7-2.7; females, OR, 2.0; 95% CI, 1.4-2.9). Higher levels of BMI were associated with increased risk (overweight males, OR, 1.8; 95% CI, 1.5-2.2; obese males, OR, 2.4; 95% CI, 1.9-3.2). The overall associations with cardia cancer were heterogeneous, although stratification by study location provided homogeneous results for populations from the United States or Europe. A high BMI was weakly associated with the risk of cardia adenocarcinoma (OR, 1.5; 95% CI, 1.3-1.8; P(heterogeneity) = 0.38). CONCLUSIONS: Pooled results from observational studies support a positive association between high BMI and the risk for esophageal and possibly for cardia adenocarcinoma.