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Background and Aims: Esophageal chromoendoscopy with iodine solution is an important diagnostic method for the detection of superficial esophageal cancer. However, the concentration of iodine solution has differed among reports. This study aimed to evaluate patient discomfort with different iodine concentrations., Methods: We performed a prospective, double-blind, randomized study. We prospectively enrolled and analyzed 77 patients who were at high risk for esophageal carcinoma and scheduled to undergo EGD from March 2018 to January 2019. All patients were divided into 2 groups before the procedure to compare pain measurements: a 1% iodine solution group (group A) and a 2% iodine solution group (group B). The primary endpoint of this study was the difference in pain measurement between 1% and 2% iodine solution chromoendoscopy. Secondary endpoints were safety, detection yield, and color evaluation based on both the endoscopist's survey and color values, as determined using the Commission Internationale de l'Eclairage (CIELAB, Vienna, Austria) color evaluation system, in the iodine-faded and iodine-stained area of each group., Results: Heartburn and retrosternal pain in group A were significantly lower than those in group B (P = .02). Eleven patients reported heartburn and retrosternal pain (group A, 2; group B, 9). Four patients reported pain above the sternal angle and 7 below the sternal angle. There was no significant difference between the 2 groups with regard to detection yield, color evaluation by the endoscopist's assessment, or color values. No patients had any adverse events, and all safely completed this study., Conclusions: The 2% iodine solution resulted in significantly greater pain than the 1% iodine solution, and the color of the stained esophageal images of each group was the same from this study. Therefore, the 1% iodine solution is recommended for esophageal chromoendoscopy. (Clinical trial registration number: UMIN 000029796.)., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)