Background: Endoscopic mucosal resection is recommended for squamous cell carcinoma of the esophagus confined to the lamina propria. However, endoscopic mucosal resection is often performed in patients with tumors that invade the muscularis mucosa or upper submucosa to minimize surgical invasiveness, despite the increased risk of lymph node metastasis. This study prospectively evaluated long-term outcome in such patients. Methods: Twenty-six consecutive patients with squamous cell esophageal carcinoma invading the muscularis mucosa or submucosa who underwent endoscopic mucosal resection from June 1992 through March 2000 (extended endoscopic mucosal resection group) were studied. As control group, 44 consecutive patients with esophageal carcinoma invading the muscularis mucosae or upper third of the submucosa and no preoperative evidence of lymph node metastasis who underwent esophagectomy during the same period (surgical resection group) were studied. Results: Overall survival rates at 5 years in the extended endoscopic mucosal resection group and surgical resection group were, respectively, 77.4% and 84.5%. There was no significant difference between survival distributions. Cause-specific survival rates at 5 years in extended endoscopic mucosal resection and surgical resection groups were, respectively, 95.0% and 93.5%. Survival curves for the groups were similar. Conclusion: Although patients were not randomized to extended endoscopic mucosal resection or surgical resection in this study, the results suggest that endoscopic mucosal resection may be safe and effective for management of squamous cell esophageal carcinoma invading the muscularis mucosae or upper submucosa. (Gastrointest Endosc 2002;56:387-90.)