Background and study aims Endoscopic full-thickness resection allows resection of early gastrointestinal neoplasms not amenable to conventional endoscopic resection techniques, due to their location, presence of submucosal fibrosis, or suspected deep mural invasion. It is typically achieved using a dedicated over-the-scope device (full-thickness resection device or FTRD). The aim of our study was to evaluate the feasibility, safety, and clinical outcomes of endoscopic full-thickness resection using an endoscopic submucosal dissection (ESD) knife. Patients and methods Consecutive patients who underwent full-thickness endoscopic resection at six tertiary care centers from August 2010 to June 2017 were retrospectively included. We conducted a comparative analysis of patient characteristics, technical success, adverse events, and time to discharge between patients treated by a full-thickness resection using an ESD knife. Results Twenty-one procedures were performed using an ESD knife. En-bloc resection and R0 resection rates were 95.2 % and 65 %, respectively. Clinical symptoms of perforation occurred in 66.7 %. There was no need for surgery or additional endoscopic procedures. Conclusion Endoscopic full-thickness resection of early colorectal neoplasms using an ESD knife might be feasible and safe. It allows complete resection of lesions with no limitation in size. The technique may be preferable to an other-the-scope resection device in lesions larger than 20 mm, and to surgery in selected cases of low-risk T1 colorectal carcinomas, non-lifting adenomas, submucosal tumors, or technically challenging lesion locations.