Animal and human models suggest associations between fat intake, fiber intake, and the risk of esophageal adenocarcinoma. We evaluated whether these factors may act early in the carcinogenic pathway as a risk factor for Barrett's esophagus, a potentially premalignant precursor to esophageal adenocarcinoma using a case-control design within the Kaiser Permanente, Northern California population. Incident Barrett's esophagus cases (n = 296) were matched to persons with gastroesophageal reflux disease (GERD) (n = 308) and to population controls (n = 309). Higher intakes of omega-3-fatty-acids [cases vs. population controls; OR = 0.46, 95% CI = 0.22-0.97, 4th vs. 1st quartiles of intake], polyunsaturated fat, total fiber (OR = 0.34, 95% CI = 0.15-0.76), and fiber from fruits and vegetables (OR = 0.47 95% CI = 0.25-0.88) were associated with a lower risk of Barrett's esophagus. Higher meat intakes were associated with a lower risk of long-segment Barrett's esophagus (OR = 0.25, 95% CI = 0.09-0.72). In contrast, higher trans-fat intakes were associated with increased risk (OR = 1.11; 95% CI = 1.03-1.21 per g/day). Total fat intake, barbecued foods, and fiber intake from sources other than fruits and vegetables were not associated with Barrett's esophagus. Future studies to evaluate whether dietary interventions might influence the risk of Barrett's esophagus or esophageal adenocarcinoma in high risk persons are needed.