Abstract Background Endoscopic mucosal resection is established for the removal of non-invasive colorectal tumours smaller than 20 mm but is unsatisfactory for larger lesions. Endoscopic submucosal dissection (ESD) enables en bloc resection of lesions larger than 20 mm. A UK-based prospective feasibility study of ESD for colorectal tumours was undertaken; primary endpoints were R0 resection, safety and recurrence. Methods Patients with Paris 0-II adenomas or laterally spreading tumours (LSTs) greater than 20 mm in diameter were enrolled between November 2004 and August 2006. Lesions were assessed by chromoscopy and high-frequency ultrasonography. Dysplasia, resection status, 30-day complication rates and recurrence after ESD were recorded. Results ESD was performed in 42 of 56 identified patients; en bloc resection was possible in 33. Fourteen Paris 0-II lesions and 28 LSTs were identified; 40 were dysplastic adenomas and two adenocarcinomas. R0 resection was achieved in 31 patients (74 per cent). The 30-day mortality rate was 0 per cent. Perforation occurred in one patient and uncomplicated bleeding in five. The 6-month cure rate was 81 per cent (34 of 42 patients). Conclusion High cure rates are achievable using ESD for Paris 0-II adenomas and LSTs greater than 20 mm in diameter, with R0 resection possible in most patients. ESD is feasible throughout the colorectum with no increase in complication rates. It should be considered for selected Tim/T1 N0 colorectal lesions.