Background and aim: The incidence of adenocarcinoma of the esophagus and esophagogastric junction has increased dramatically in many Western countries. An important risk factor, gastroesophageal reflux disease, causes inflammation and increased production of oxygen free radicals in the esophageal mucosa. These radicals can produce a promutagenic DNA lesion, 8-hydroxydeoxyguanosine (8-OH-dG), linked to carcinogenesis in several malignancies. We examined alterations in the oxidative DNA damage (8-OH-dG) in Barrett’s mucosa with and without associated adenocarcinoma or high-grade dysplasia compared to normal control’s squamous mucosa. Patients and methods: We measured oxidative DNA damage (8-OH-dG) in 46 patients: 13 Barrett’s metaplasia, 24 adenocarcinoma or high-grade dysplasia of distal esophagus/esophagogastric junction, and 9 normal controls. The formation of 8-hydroxydeoxyguanosine was determined using routine liquid chromatography. All samples were taken either at endoscopy, or, during surgery, from resected specimen. The average 8-OH-dG concentration was expressed as the ration of 8-OH-dG per 10⁵ deoxyguanosine ± standard error of mean. Results: Analysis revealed significantly increased oxidative DNA damage (8-OH-dG) in the distal esophagus in both Barrett’s epithelium (3.19±1.75) and adenocarcinoma/high-grade dysplasia (1.23±0.07) compared to controls (0.77±0.47), p=0.02 for both. In patients with Barrett’s mucosa, no significant difference existed in 8-OH-dG levels between samples from distal and proximal esophagus. Conclusions: Oxidative DNA damage (8-OH-dG) is increased significantly in malignant transformation of Barrett’s esophagus and seems to play an important role in the carcinogenesis of esophageal mucosa.