Background and study aim: Data are limited on the natural history of patients with Barrett's esophagus with a diagnosis of indefinite for dysplasia (IND). The aims of this study were to: (i) determine rates of progression to high grade dysplasia (HGD) or esophageal adenocarcinoma, and compare these with rates for low grade dysplasia (LGD); and (ii) determine the proportion of patients whose histological IND diagnosis changed on follow-up endoscopy. Patients and methods: Demographic, endoscopic, and histologic information of patients with diagnoses of IND and LGD and at least 12 months of follow-up were extracted from the database of a multicenter Barrett's esophagus study. Rates and times for progression to HGD and esophageal adenocarcinoma and regression to nondysplastic epithelium were calculated. Proportions of diagnoses upgraded to HGD/esophageal adenocarcinoma or downgraded to nondysplastic epithelium at first follow-up endoscopy were evaluated. Results: Amongst 2264 patients, 83 with a diagnosis of IND (mean age 60 years, 95% men, 95% white; mean follow-up 5.6 years) and 79 with diagnosis of LGD were identified. In the IND group, annual incidences of esophageal adenocarcinoma and HGD were 0.21% and 0.64%, respectively, representing a combined incidence of 0.8%. Mean time to progression was 4.72 years. Within the IND group 55% patients showed regression to nondysplastic epithelium at first follow-up endoscopy and the overall regression rate was 80%. Corresponding rates in LGD patients were similar. Conclusions: Lesions diagnosed as IND and LGD show similar biological behavior and can be treated as a single category with respect to surveillance and follow-up.