Objective: Esophageal endoscopic submucosal dissection (ESD) requires more skill than gastric ESD. To perform esophageal ESD safely, we used a sodium hyaluronate solution (MucoUp) as the endoscopic submucosal injection material, and the stag beetle (SB) knife as the main device for esophageal ESD. Our aim was to evaluate the clinical safety and efficiency of MucoUp and the SB knife for esophageal ESD. Method: A total of 84 patients with 110 esophageal lesions who were treated with ESD from January 2013 to June 2016 were analyzed. The lesions were evaluated using magnifying endoscopy with narrow-band imaging and chromoendoscopy with Lugol’s solution. All diagnoses were confined with histologic evaluation through biopsy. Prior to ESD, routine blood tests and computed tomography to evaluate lymph node and distant metastasis were performed for all patients. In addition, the tumor invasion depth was evaluated as necessary, using endoscopic ultrasound. All ESD procedures used MucoUp as the submucosal injection material and the SB knife as the main device for esophageal ESD. Result: There were 78 male and 6 female patients, and average age was 69.7 years (range, 50 to 87 years). There were 19 patients with 45 multiple lesions (13 patients with 2 lesions, 5 patients with 3 lesions, and 1 patient with 4 lesions). Four lesions were excluded because they were diagnosed as nonepitherial tumors (leiomyoma in 2, granular cell tumor in 1 and undetermined in 1). The mean tumor size was 40.4 mm (range, 13 mm to 122 mm). A mean operative time was 45.3 min (range, 8 min to 132 min). The mean 3.9 vials (range, 2 to 12 vials) of MucoUp were used. The en bloc resection rate and R0 resection rate were 100% and 92.7%, respectively. There were no significant complications such as perforation, bleeding, or mediastinal emphysema. Postoperative esophageal stricture occurred in eight patients, all of whom were treated with endoscopic balloon dilation. Conclusion: MucoUp and the SB knife are safe and effective agents that are useful for submucosal injection and do not cause any significant adverse events during endoscopic submucosal dissection.