BACKGROUND: The rate of occult adenocarcinoma at esophagectomy in patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) has been reported to be approximately 40%. Recently, it has been suggested that this risk may be overestimated. OBJECTIVE: Our purpose was to determine the rate of submucosal invasive adenocarcinoma in patients undergoing esophagectomy for BE after biopsy diagnosis of HGD or intramucosal carcinoma (IMC). A secondary aim was to identify clinical risk factors for submucosal invasive adenocarcinoma in these patients. DESIGN: A retrospective study. SETTING: Tertiary referral center. PATIENTS: All patients with preoperative BE with HGD or IMC treated with esophagectomy over a 20 year period. INTERVENTIONS: Esophagectomy. MAIN OUTCOME MEASUREMENTS: Submucosal invasive adenocarcinoma at esophagectomy. RESULTS: Sixty patients were included (41 with preoperative HGD, 19 with preoperative IMC). The overall rate of submucosal invasive carcinoma was 6.7% (95% CI, 1.8%-16.2%) (n = 4), with a 5% rate of submucosal invasion in patients with preoperative HGD and 11% for patients with preoperative IMC. All 4 patients with submucosal invasion at esophagectomy had either nodular or ulcerated mucosa on preoperative endoscopy. The 1-year and 5-year all-cause risks of death for the entire cohort were 1.9% and 10.9%, respectively. LIMITATIONS: Retrospective study. CONCLUSIONS: The rate of submucosal invasive adenocarcinoma at esophagectomy in BE patients with HGD or IMC on biopsy is much lower than 40%. After adequate sampling and staging, patients with BE with HGD and IMC, especially those without endoscopically visible lesions, can potentially be treated by nonsurgical (local) therapies.