A narrow band imaging (NBI) endoscopy system has been developed that allows superficial surface imaging of esophageal tissue in vivo. The objective was to assess the potential of NBI for prediction of histology during screening and surveillance endoscopy in patients with Barrett's esophagus (BE). A prospective cohort study. Veterans Affairs Medical Center. Fifty-one patients with known or suspected BE. NBI images were graded according to mucosal pattern (ridge/villous, circular and irregular/distorted) and vascular pattern (normal and abnormal), and correlated with histology in a prospective, blinded manner. Biopsy-confirmed intestinal metaplasia (IM) and dysplasia were used as the outcome measures. Of 51 patients (mean BE length 3.5 cm), 28 had IM without dysplasia, 8 had low-grade dysplasia (LGD), 7 had high-grade dysplasia (HGD), and 8 had cardiac-type mucosa. The sensitivity, specificity, and positive predictive value of ridge/villous pattern for diagnosis of IM without HGD were 93.5%, 86.7%, and 94.7%, respectively. The sensitivity, specificity, and positive predictive value of irregular/distorted pattern for HGD were 100%, 98.7%, and 95.3%, respectively. If biopsies were limited to areas with irregular/distorted pattern, no patient with HGD would have been missed. However, NBI was unable to distinguish areas of IM from those with LGD. The open study design without a control group was the main limitation. NBI is a novel diagnostic tool with a high degree of accuracy for the detection of metaplastic and dysplastic tissue within the BE segment.