Due to the implementation of colorectal cancer (CRC) screening programs, complex colorectal polyps and early colorectal cancers (T1 CRC) are increasingly detected in clinical practice. The central theme of this thesis is the optimization of endoscopic treatment for complex colorectal polyps and T1 CRC. The first part of this thesis (chapter 2-4) focuses on a new endoscopic resection technique called endoscopic full-thickness resection (eFTR). This is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions unsuitable to conventional endoscopic resection. By performing a transmural resection of the colonic wall, eFTR can overcome limitations posed by submucosal scarring or non-lifting of conventional endoscopic resection methods with the potential to avoid a surgical resection. The second part of this thesis (chapter 5-6) reports on improvements in endoscopic treatment strategies as well as the standardization of AEs. To facilitate peer consultation and optimize care for patients with complex colorectal polyps, we initiated in chapter 5 an expert panel in the northwestern region of the Netherlands. In chapter 6 a novel classification for adverse events in gastrointestinal endoscopy is proposed: the AGREE classification. The third part focusses on further refinement of T1 CRC treatment. The depth of submucosal invasion was for long considered an important risk factor for LNM. In chapter 7 we performed a meta-analysis to evaluate whether DSI is a significant independent risk factor for LNM in T1 CRC. Finally, in chapter 8 of this thesis a prospective multicenter trial protocol is described, that will assess long term oncological safety of completion eFTR, following incomplete endoscopic resection of low-risk T1 CRC.