Metaplastic glands buried under squamous epithelium are frequently detected in patients with Barrett’s esophagus (BE). This sub-squamous intestinal metaplasia (SSIM) might be responsible for cancers that develop despite endoscopic surveillance, and for metaplasia recurrences after endoscopic ablation. To determine whether reflux induces BE cells to undergo epithelial to mesenchymal transition (EMT) that produces SSIM, we assessed EMT in BE cells exposed to acidic bile salts, and in rat and human esophageal tissues.