Barrett’s esophagus (BE) and associated adenocarcinoma have emerged as a major health care problem over the last two decades. Because of the widespread use of endoscopy, BE is being recognized increasingly in all Western countries. In clinical trials of endoscopic optical coherence tomography (EOCT), we defined certain image features that appear to be characteristic of precancerous (dysplastic) mucosa: decreased scattering and disorganization in the microscopic morphology. The objective of the present work is to develop computer-aided diagnosis (CAD) algorithms that aid the detection of dysplasia in BE. The image dataset used in the present study was derived from a total of 405 EOCT images (13 patients) that were paired with highly correlated histologic sections of corresponding biopsies. Of these, 106 images were included in the study. The CAD algorithm used was based on a standard texture analysis method (center-symmetric auto-correlation). Using histology as the reference standard, this CAD algorithm had a sensitivity of 82%, specificity of 74%, and accuracy of 83%. CAD has the potential to quantify and standardize the diagnosis of dysplasia and allows high throughput image evaluation for EOCT screening applications. With further refinements, CAD could also improve the accuracy of EOCT identification of dysplasia in BE.