Background Many novel image-enhanced and magnified endoscopies including NBI, Fuji intelligent color enhancement (FICE) and confocal laser endoscopy (CLE) are superior to standard white light endoscopy (WLE) in detecting subtle lesions. Minimal change esophageal reflux disease (MERD) is diagnosed by positive symptoms of acid regurgitation or heartburn with negative WLE study but positive image-enhanced study. For MERD diagnosis, the new FICE is aimed at detecting a small mucosal break and subtle inflammatory changes. CLE is aimed at detecting the inflammatory change of esophagus by demonstrating the increased number of intrapapillary capillary loop (IPCL). To date, there has been no direct comparison between FICE and probe based confocal laser endoscopy (pCLE) in diagnosing MERD. Objective To compare the feasibility of FICE and pCLE for MERD detection. Method Thirty-six patients with MERD (typical reflux symptom, positive GerdQ ≥8 and no mucosal break on WLE more than 5 mm) and eighteen asymptomatic subjects (control) were recruited. The new FICE (EPX-4450HD) was performed at non-magnified, x50, and x100 zoom levels under the station 0 (RGB 525,495,495), 1 (RGB 550,500,470), 5 (RGB 560,500,475), and 8 (RGB 540,505,420). The criteria for positive FICE were; A) triangular indentation, B) punctuate erythema, C) villiform mucosa, and D) increased number of capillary vessel. At the same session, pCLE was applied to count the number of IPCL by using more than 5/ 500x500 micron (4 sets of pCLE view) as a criterion for MERD diagnosis. Endoscopic findings by FICE and pCLE were interpreted right away during the endoscopic examination. Results No difference between pCLE and over all FICE criteria in diagnosing MERD ( McNemar test, P = 0.594 ) and revealed increase capillary loop criteria also no difference between FICE and pCLE. From the new FICE, the overall accuracy, sensitivity, specificity, PPV, and NPV were 79%,94%, 50%, 79% and 82%, respectively. In contrast, pCLE revealed 87% accuracy, 97% sensitivity, 66% specificity, 85% PPV and 92% NPV. Conclusions FICE and pCLE are useful for MERD detection. Overall FICE criteria showed no different from pCLE when diagnosis of MERD by counting the number of IPCL> 5/500x500 micron. Increased number of capillary vessel are more sensitive than the other three FICE criteria in diagnosing MERD. However, using all 4 FICE criteria is more sensitive than using one criterion. pCLE criteria provides more accuracy in diagnosing MERD than the overall FICE criteria.