Background and Study Aims: The technique of endoscopic submucosal dissection (ESD) has recently been developed for en-bloc resection of gastric tumors. For oncological reasons and in order to improve the patients’ quality of life, it may be desirable to use the same technique for rectal neoplasia. Patients and Methods: Thirty-five consecutive patients with rectal neoplasia who had a preoperative diagnosis of large intraepithelial neoplasias with submucosal fibrosis or located on the rectal folds were enrolled. ESD was carried out with the same technique previously described for the stomach, with some modifications. The efficacy, complications, and follow-up results of the treatment were assessed. Results: The rates of en-bloc resection and en-bloc plus R0 resection were 88.6 % (31 of 35) and 62.9 % (22 of 35), respectively. Hemoglobin levels did not drop by more than 2 g/dl in any of the patients after ESD. None of the patients had to receive blood transfusions or undergo emergency colonoscopy due to bleeding during ESD or hematochezia after ESD. Perforation during ESD occurred in two patients (5.7 %), who were managed with conservative medical treatment after endoscopic closure of the perforation. Excluding three patients in whom additional surgery was carried out, all but one of 32 patients were free of recurrence during a mean follow-up period of 36 months (range 12 - 60 months). The exception was a patient in whom a multiple-piece resection was required; the recurrent (residual) tumor, found 2 months after ESD, was a small adenoma that was again treated endoscopically. Conclusions: ESD is applicable in the rectum with promising results, but the technique is still at a developmental stage and patients should be informed of the potential risks.