A novel endoluminal fundoplication (ELF) technique using a trans-oral and fastener-deploying device (EsophyX, EndoGastric Solutions) was developed and evaluated for feasibility, safety and the treatment of gastroesophageal reflux disease (GERD) in a series of bench, animal, human (phase 1, phase 2, commercial registry) studies. The studies verified biological compatibility, durability and non-toxicity of the polypropylene fasteners as well as the feasibility of the ELF technique. The results of the preclinical testing indicated that the EsophyX device was shown to be safe, and capable of deploying fasteners directly into tissue and forming an interrupted suture line at the base of the gastro-esophageal valve (GEV). Moreover, the studies demonstrated that the ELF technique performed using the EsophyX device resulted in the creation of new GEVs of 3-5 cm in length and a circumference of 200 degrees -310 degrees , which maintained their anatomical aspects at six months. The ELF-created GEVs appeared similar to those created by laparoscopic anti-reflux surgery (LARS). The ELF procedure also resulted in reduction of all small hiatal hernias (2 cm in size) and restoration of the angle of His. The ELF procedure provides an anatomical approach similar to that of LARS for the treatment of GERD.