Background: Barrett's oesophagus develops in some individuals with gastro-oesophageal reflux and is the precursor to oesophageal adenocarcinoma. Proton pump inhibitors (PPIs) suppress gastric acid production and are used to treat reflux. Clinical trials suggest that cyclooxygenase (COX) inhibitors might prevent oesophageal cancer, although PPIs could offset this by increasing COX-2 expression in Barrett's oesophagus. To investigate this, we evaluated the impact of a PPI on COX expression in oesophageal mucosal cells. Methods: The effect of the PPI esomeprazole on COX-1 and COX-2 mRNA levels in oesophageal cells was determined. Oesophageal cell lines OE33 (adenocarcinoma-derived) and HET-1A (immortalized squamous cells) and a control intestinal cell line HT29 (colon carcinoma) were treated for 24h, with increasing concentrations of the esomeprazole. Results: COX-2, but not COX-1, mRNA levels dose-dependently increased in OE33 and HET-1A cells versus esomeprazole concentration. COX-2 mRNA levels did not increase in HT29 cells. Conclusions: Exposure to esomeprazole increases COX-2 mRNA in oesophageal cells. This might contribute to the lack of benefit for COX inhibitors for oesophageal cancer prevention in recent clinical studies.