© 2015 American Society for Gastrointestinal Endoscopy. Background Endoscopic therapy is the preferred approach for the management of Barrett's esophagus (BE) patients with high-grade dysplasia (HGD) and intramucosal carcinoma (IMC). Little is known about outcome differences in patients with HGD versus IMC. Objective To determine and compare the rate of recurrent dysplasia or neoplasia in patients with HGD or IMC undergoing endoscopic therapy. Design Retrospective cohort study. Patients A total of 246 BE patients with either HGD or IMC referred for endoscopic therapy. Intervention Patients underwent EMR and/or ablation therapy with the goal of complete eradication of all dysplasia/neoplasia and intestinal metaplasia (CE-IM). Patients were assigned to either the HGD or IMC group based on highest pathology grade at the start of therapy. Main Outcome Measurements Complete eradication and recurrence of IM and/or HGD/neoplasia were assessed among patients with HGD versus IMC. Only patients with CE-IM (documented eradication of all dysplasia/neoplasia and IM on a single endoscopy) were included for analysis of recurrence rates and risk factors. Results CE-IM was achieved in 113 of 135 patients (83.7%) with HGD and in 84 of 111 patients (75.7%) with IMC (P =.16). Overall recurrence rates of dysplasia or neoplasia after CE-IM were similar in both groups (HGD, 8.0% vs IMC, 9.5%; P =.44; relative risk, 1.2; 95% confidence interval, 0.5-3.0) and remained similar in patients with 5 years of surveillance after CE-IM (HGD, 13.5% vs IMC, 11.4%; P =.53; relative risk, 0.85; 95% confidence interval, 0.3-2.7). Limitations Retrospective, observational study and evolution of endoscopic modalities and experience. Conclusion Endoluminal therapy can successfully achieve eradication of IM and dysplasia or neoplasia in BE patients with HGD and IMC at comparable rates. There were no differences in the rates of recurrent HGD/IMC in the 2 groups.