OBJECTIVE: To investigate the association between selenium and the risk of Barrett's esophagus (BE), the precursor lesion of esophageal adenocarcinoma. METHODS: Data from the prospective Netherlands Cohort Study were used. This cohort study was initiated in 1986, when 120,852 subjects aged 55-69 years completed a questionnaire on dietary habits and lifestyle, and provided toenail clippings for the determination of baseline selenium status. After 16.3 years of follow-up, 253 BE cases (identified through linkage with the nationwide Dutch pathology registry) and 2,039 subcohort members were available for case-cohort analysis. Cox proportional hazards models were used to calculate incidence rate ratios (RR). RESULTS: The multivariable-adjusted RR for the highest versus the lowest quartile of toenail selenium was 1.06 (95% CI 0.71-1.57). No dose-response trend was seen (p trend = 0.99). No association was found in subgroups defined by sex, smoking status, body mass index (BMI), or intake of antioxidants. For BE cases that later progressed to high-grade dysplasia or adenocarcinoma, the RR for a selenium level above the median vs. below the median was 0.64 (95% CI 0.24-1.76). CONCLUSIONS: In this large prospective cohort study, we found no evidence of an association between selenium and risk of BE.