Abstract Abstract Background: Endoscopic submucosal dissection (ESD) has recently been developed for endoscopic treatment of GI tumors, which enables us to resect even large tumors en bloc. However, a considerable frequency of perforation has become another problem. The best way to prevent perforation is to create a sufficient submucosal fluid cushion (SFC). The aim of this study is to find out the feasibility of ESD by using a mixture of 1900 KDa hyaluronic acid (Suvenyl) and a 10% glycerin plus 5% fructose solution (Glyceol). Methods: Sixty-seven consecutive GI tumors in 54 patients who met indication criteria of ESD were enrolled. The mixing ratios of Suvenyl and Glyceol were 1∶ 3 for esophageal/colorectal tumors and stomach tumors with scar, and 1∶ 7 for stomach tumors without scar. After creation of SFCs, mucosal incision around the tumors and submucosal dissection under the tumors were made by cutting devices. The clinical outcomes were investigated. Results: Mean resected and tumor sizes were 38.6 and 25.6 mm, respectively. Perforation occurred in one colon tumor with severe fibrosis (1.5% ), which was managed by endoscopic clipping without salvage surgery. No blood transfusion was performed. In one stomach and in one rectal tumor (3% ), endoscopic hemostasis was necessary because of post-operative bleeding. Overall endoscopic and histologic en bloc resection rates were 94% (63/67) and 78% (52/67), respectively, and there was no recurrence after follow-up of 1 year. Conclusions: ESD when using a mixture of Suvenyl and Glyceol results in excellent outcomes, and this injection solution should be used for ESD. Abstract Abstract Background: Endoscopic submucosal dissection (ESD) has recently been developed for endoscopic treatment of GI tumors, which enables us to resect even large tumors en bloc. However, a considerable frequency of perforation has become another problem. The best way to prevent perforation The aim of this study is to find out the feasibility of ESD by using a mixture of 1900 KDa hyaluronic acid (Suvenyl) and a 10% glycerin plus 5% fructose solution (Glyceol) is to create a sufficient submucosal fluid cushion . Methods: Sixty-seven consecutive GI tumors in 54 patients with met indication criteria of ESD were enrolled. The mixing ratios of Suvenyl and Glyceol were 1: 3 for esophageal / colorectal tumors and stomach tumors with scar, and 1: 7 for stomach tumors without scar. After creation of SFCs, mucosal incision around the tumors and submucosal dissection under the tumors were made by cutting devices. In a stomach and in one rectal tumor (1.5%), which was managed by endoscopic clipping without salvage surgery. No blood transfusion was performed. 3%), endoscopic hemostasis was necessary because of post-operative bleeding. Overall endoscopic and histologic en bloc resection rates were 94% (63/67) and 78% (52/67), respectively, and there was no recurrence after follow- up of 1 year. Conclusions: ESD when using a mixture of Suvenyl and Glyceol results in excellent outcomes, and this injection solution should be used for ESD.