OBJECTIVE: The incidence of esophageal adenocarcinoma has been increasing rapidly among many countries. Antioxidant intake is a potentially modifiable protective factor, although the results from individual studies are inconclusive. We conducted a systematic review and statistical synthesis of studies that evaluated the associations between vitamin C, vitamin E, or beta-carotene/vitamin A and the risk of esophageal adenocarcinoma or the adjacent gastric cardia (gastroesophageal junction) adenocarcinoma. METHODS: Studies were included if they reported (a) a measure of dietary antioxidant intake; (b) esophageal or cardia adenocarcinoma occurrence; and (c) a relative risk or odds ratio (OR) with confidence intervals (CI), or sufficient data to permit their calculation. RESULTS: We identified 10 studies (1 cohort, 9 case-control; 1,057 esophageal and 644 cardia cases). Summary estimates stratified by cancer site suggested that higher intakes of vitamin C, beta-carotene/vitamin A, and vitamin E were inversely associated with the risk of esophageal adenocarcinoma (vitamin C, OR 0.49, 95% CI 0.39-0.62, P(heterogeneity)= 0.10; beta-carotene, OR 0.46, 95% CI 0.36-0.59, P(heterogeneity)= 0.82; vitamin E intake, OR 0.80, 95% CI 0.63-1.03, P(heterogeneity)= 0.59). Beta-carotene intake was also inversely associated with the risk of cardia adenocarcinoma (OR 0.57, 95% CI 0.46-0.72, P(heterogeneity)= 0.17). Dose effects were observed for most associations. CONCLUSIONS: Pooled results from observational studies suggest that antioxidant intake may be protective against esophageal adenocarcinoma; the data do not support a consistent association between antioxidant intake and the risk of cardia carcinoma. These findings suggest possible etiological differences between these two adjacent malignancies.