BACKGROUND & AIMS: High-resolution endoscopy with narrow band imaging (NBI) enhances the visualization of mucosal glandular and vascular structures. This study assessed whether narrow band targeted biopsies could detect advanced dysplasia using fewer biopsy samples compared with standard resolution endoscopy. METHODS: We conducted a prospective, blinded, tandem endoscopy study in a tertiary care center with 65 patients with Barrett's esophagus undergoing evaluation for previously detected dysplasia. Standard resolution endoscopy was used first to detect visible lesions. Narrow band endoscopy was then used by another gastroenterologist to detect and biopsy areas suspicious for dysplasia. The lesions initially detected by standard resolution endoscopy were then disclosed and biopsied, after biopsy of the lesions targeted with NBI. Finally, random 4-quadrant biopsies were taken throughout the segment of Barrett's mucosa. RESULTS: Higher grades of dysplasia were found by NBI in 12 patients (18%), compared with no cases (0%) in whom standard resolution white light endoscopy with random biopsy detected a higher grade of histology (P < .001). Correspondingly, narrow band directed biopsies detected dysplasia in more patients (n = 37; 57%) compared with biopsies taken using standard resolution endoscopy (n = 28; 43%). In addition, more biopsies were taken using standard resolution endoscopy with random biopsy compared with narrow band targeted biopsies (mean 8.5 versus 4.7; P < .001). CONCLUSIONS: In patients evaluated for Barrett's esophagus with dysplasia, NBI detected significantly more patients with dysplasia and higher grades of dysplasia with fewer biopsy samples compared with standard resolution endoscopy.