Objectives: Patients with Barrett's high-grade dysplasia (HGD) or early esophageal adenocarcinoma (EAC) that is shown on biopsy alone continue to undergo esophagectomy without more definitive histological staging. Endoscopic resection (ER) may provide more accurate histological grading and local tumor (T) staging, definitive therapy, and complete Barrett's excision (CBE); however, long-term outcome data are limited. Our objective was to demonstrate the effect on histological grade or local T stage, efficacy, safety and long-term outcome of ER for Barrett's HGD/EAC and of CBE in suitable patients.Methods: This prospective study at two Australian academic hospitals involved 75 consecutive patients over 7 years undergoing ER for biopsy-proven HGD or EAC, using multiband mucosectomy or cap technique. In addition, CBE by 2-3-stage radical mucosectomy was attempted for all Barrett's segments 3 cm in length in patients aged <75 years with minimal comorbidities.Results: Biopsy histology showed HGD in 89% of patients and EAC in 11%. However, ER histology resulted in altered grading or staging in 48% of patients (down 28%, up 20%), with HGD in 53%, low-grade dysplasia (LGD) in 19%, mucosal adenocarcinoma in 13%, submucosal adenocarcinoma in 9%, and no dysplasia in 4% of patients. The CBE success rate was 94%. Complications were one aspiration (hospitalization with full recovery) and six strictures successfully dilated endoscopically. During the mean follow-up of 31 months (range 3-89), there was no recurrence at ER sites, 11% developed metachronous lesions and five patients underwent esophagectomy for ER-demonstrated submucosal invasion. Esophagectomy specimens were T0N0M0 in three and T1N0M0 in two patients. There were no deaths due to adenocarcinoma.Conclusions: ER alters histological grade or local T stage in 48% of patients and dramatically reduces esophagectomy rates by providing safe and effective therapy. ER has a high success rate (94%) for CBE in short segment Barrett's esophagus.