Background: The introduction of bowel cancer screening programs has led to an increasing incidence of complex colonic polyps and early colonic cancer requiring colectomy. Traditional radical colonic resection risks substantial morbidity and there is a need for alternative approaches. This review summarizes the published methods of colonic endoscopic full-thickness resection (EFTR), examining data on feasibility and safety. Preclinical research reported on three EFTR techniques using endoscopic stapling devices, T-tags or compression device closure for defect closure before or after specimen resection. A total of 103 procedures were performed in 99 porcine models, with an overall success rate of 87% (90/103 procedures). The intraoperative complication rate was 19% (19/90 procedures). When bowel closure was performed after resection, rather than before it, it more commonly resulted in failure to close the defect and a high incidence of abnormal findings at post-mortem examination. Clinical experience involved five studies reporting EFTR in 38 patients, with three of these using compression device pre-resection closure and one, post-resection closure. EFTR was completed in 33/38 without assistance. Only three patients had complications reported. Lateral margin clearance was variably reported and complete full-thickness resection was achieved in only 12/17 patients. The technique of EFTR is evolving, with only limited clinical evidence to date, but currently pre-resection closure methods seem advisable. Significant technological challenges remain, including reproducible lateral margin clearance. before colonic EFTR can be recommended.