Although there have been earlier reports on the use of three-dimensional endoscopic systems in the gastrointestinal tract, real-time three-dimensional imaging has not previously been described. This paper presents experience in three cases with a novel endoscopic system for three-dimensional observation in clinical situations. Case 1 was a hyperplastic gastric polyp, the shape of which was considerably enhanced in comparison with two-dimensional endoscopic viewing. Case 2 was an advanced esophageal cancer, in which the sense of depth was improved in the esophagus. Case 3 was a depressed early gastric cancer, the shape of which was also enhanced. Between July 2001 and March 2002, three experienced endoscopists also used this new system in a further 34 patients. A three-dimensional endoscopic environment was visible with the system in all patients, and all of the endoscopists were able to obtain visual information regarding spatial depth. This experience suggests that the three-dimensional video-endoscopic system used here can be of value in gastrointestinal endoscopy.