Recent clinical data have revealed that mixed reflux (MR) of gastric acid and duodenal contents frequently occurs in patients with gastroesophageal reflux disease and a progressive increase of MR occurs with increasing severity across gastroesophageal reflux disease. Herein we report a novel rat surgical model in which esophageal metaplasia and adenocarcinoma develop as complications of MR. The model was created by performing an esophagojejunostomy and a gastrojejunostomy 5 mm proximal to the esophagojejunal anastomosis in 40 rats. Severe inflammatory and proliferative changes, high prevalence of esophageal metaplasia (78%), and adenocarcinoma (50%) were observed in the lower part of the esophagus of rats 20 weeks after surgery. The resulting esophageal lesions resembled those described in humans and supported a progression from intestinal metaplasia to dysplasia and, ultimately, esophageal adenocarcinoma. Such a model may provide a useful tool in study of human reflux-induced carcinogenesis.