The diagnostic value of an endoscopic examination of the upper gastrointestinal, the identification of foci of early neoplasia, inflammatory diseases for a long time depended on the correctness of the selected section of the mucosa for biopsy. The risk of skipping the pathology of the esophagus and stomach mucosa remains high. Probe based confocal laser endomicroscopy (PBCLEM) is a new technology that allows real-time imaging at the cellular level using miniature optical systems, built into the tip of a small probe. Objective. Evaluation of the effectiveness of PBCLEM as a screening method in the diagnosis of diseases of the esophagus, stomach, and duodenum. Material and methods. The study included 60 patients who underwent video esophagogastroduodenoscopy, the final stage of which was PBCLEM with targeted biopsy. A comparison of the data of macroscopy, endomicroscopy with the findings of histological studies. Results. When conducting PBCLEM revealed a pathology: Epithelial neoplasms of the stomach, duodenum, Barrett esophagus, inflammatory diseases of the esophagus, stomach. Conclusion. Based on the study, it can be argued that PBCLEM, as a screening method for standard gastrointestinal endoscopy, has high specificity, sensitivity and accuracy in the diagnosis of inflammatory diseases of the upper gastrointestinal, metaplastic changes in the esophagus mucosa, and differential diagnosis of epithelial neoplasms.