BACKGROUND:Delayed postpolypectomy bleeding occurs more frequently after hot resection than after cold resection. OBJECTIVE:To elucidate the underlying mechanism, we performed a histological comparison of tissue after cold and hot snare resections. DESIGN:This is a prospective study, registered in the University Hospital Medical Information Network (UMIN000020104). SETTING:This study was conducted at Aizu Medical Center, Fukushima Medical University, Japan. PATIENTS:Fifteen patients scheduled to undergo resection of colorectal cancer were enrolled. INTERVENTION:On the day before surgery, 2 mucosal resections (hot and cold) of normal mucosa were performed on each patient using the same snare without saline injection. The difference was only the application of electrocautery or not. Resection sites were placed close to the cancer to be included in the surgical specimen. MAIN OUTCOME MEASURES:The primary outcome measure was the depth of destruction. Secondary outcome measures included the width of destruction, depth of the remaining submucosa, and number of vessels remaining at the resection sites. The number and diameter of vessels in undamaged submucosa were also evaluated. RESULTS:All cold resections were limited to the shallow submucosa, whereas 60% of hot resections advanced to the deep submucosa and 20% to the muscularis propria (p < 0.001). There was no significant difference in the width of destruction. The number of remaining large vessels after hot resections trended toward fewer (p = 0.15) with a decreased depth of remaining submucosa (p = 0.007). In the deep submucosa, the vessel diameter was larger (p < 0.001) and the number of large vessels was greater (p = 0.018). LIMITATIONS:Histological assessment was not blinded to the 2 reviewers. Normal mucosa was used instead of adenomatous tissue. CONCLUSIONS:Hot resection caused damage to deeper layers involving more large vessels. This may explain the mechanism for the reduced incidence of hemorrhage after cold snare polypectomy. See Video Abstract at http://links.lww.com/DCR/A631.