BACKGROUND AND STUDY AIMS: There have been no multicenter studies investigating the use of magnification chromoendoscopy (MCE) for the detection of intestinal metaplasia and dysplasia/cancer in Barrett's esophagus. Our aims were to assess the ability of MCE to predict the histological diagnosis (non-biopsy detection), to compare the yield of MCE-targeted versus random biopsies for dysplasia, and to compare procedure times. PATIENTS AND METHODS: In this prospective multicenter study, patients with known or suspected Barrett's esophagus underwent MCE with indigo carmine dye staining. Three mucosal patterns (ridge/villous, circular, and irregular/distorted) were standardized, based on past experience. Mucosal patterns were noted and target biopsies were obtained only if irregular/distorted patterns were identified. Otherwise, random four-quadrant biopsies were obtained. RESULTS: A total of 56 patients (mean age 64 years, mean length of Barrett's esophagus 2.7cm) were prospectively evaluated: 38 patients (67.8 %) had ridge/villous patterns, four patients (7.1 %) had circular patterns, four patients (7.1 %) had irregular/distorted patterns, and ten patients (17.8 %) had a combination of patterns. Histologically, intestinal metaplasia was not shown in eight patients (14.2 %), nondysplastic Barrett's esophagus was diagnosed in 30 patients (53.5 %), low-grade dysplasia was detected in 12 patients (21.4 %), and high-grade dysplasia was detected in six patients (10.7 %). An irregular/distorted pattern either throughout the entire segment of Barrett's esophagus or in combination with a ridge/villous or circular pattern had a sensitivity or 83 %, a specificity of 88 %, a positive predictive value of 45 %, and a negative predictive value of 98 % for high-grade dysplasia. The yield of high-grade dysplasia was similar for the two techniques but the time taken to perform MCE was less than the time taken to perform random biopsies. CONCLUSION: An irregular/distorted pattern is specific for high-grade dysplasia and so it may not be necessary to perform biopsies in patients with ridge/villous or circular mucosal patterns.