The Gatekeeper Reflux Repair System is a new, promising endoscopic anti-reflux therapy. It has now been shown that it is possible to implant hydrogel prosthesis in the submucosa of the esophagus of humans. The pilot study in humans showed that it is a safe technique and no prostheses migrated into the mediastinum. With the help of endoscopic ultrasonography, each prosthesis was followed during the 6-month pilot study. After finishing this pilot study, new multi-center studies have been initiated with implantation of more prostheses to increase efficacy. One of the definite advantages over the other endoscopic treatments currently being developed is its reversibility. Regarding endoscopic anti-reflux therapy in general, it is important to stress that at this time no data are available in the literature about the comparison to medical therapy. At the same time long-term results are also unknown. For these reasons these endoscopic procedures must be considered experimental and they should be performed in a clinical research setting. Within a few years the role of the Gatekeeper Reflux Repair System will be better understood for those PPI-dependent GERD-patients who wish to stop their medication.