Recently, duodenal tumors have been detected more often due to technical progress and the development of endoscopic instruments. However, no standard endoscopic diagnostic criteria or therapeutic strategies for duodenal epithelial tumors have been established. Radical resection techniques such as pancreaticoduodenectomy should be avoided, if possible, for treating non-invasive duodenal cancer or adenoma, because they cause more serious postoperative dysfunction in the duodenum than in other parts of the gastrointestinal tract. Endoscopic submucosal dissection (ESD) yields higher rates of en bloc resection and curative resection than endoscopic mucosal resection, and these advantages explain the lower rates of residual and recurrent tumors seen after ESD. However, it is more difficult to perform ESD for duodenal tumors than for gastric tumors, as the muscle layer of the duodenum is thinner than that in other parts of the gastric tract, which results in relatively higher frequencies of perforation and bleeding. Here, we report our experience with duodenal ESD. Closure of post-ESD duodenal artificial ulcers is very effective for avoiding delayed bleeding and perforation. We consider that post-ESD ulcer closure using a loop snare and clipping is one of the most effective ways of preventing delayed perforation. Duodenal ESD requires a high level of skill due to its technical difficulty and the increased risk of perforation associated with the procedure ; however, we consider that it is very effective. In addition, ESD is less invasive than open surgery.