Gastroesophageal reflux disease (GERD) is caused by recurring reflux of the stomach contents into the esophagus, which results in the classic symptoms of heartburn. GERD affects 25% to 40% of the world population. This chronic disorder is associated with significant morbidity, substantially impacting quality of life (QOL), and the possibility of mortality from complications. Initially GERD is treated with lifestyle modification, and dietary changes. If symptoms are persistent, drug therapy including acid suppressants and antacids, histamine-2 receptor antagonists, or proton pump inhibitors are prescribed. The pharmaceutical agents can lose their effectiveness over time, requiring progressively higher dosing. Adults affected by GERD who no longer respond adequately to drugs or those who wish to discontinue use of these medications have the option of laparoscopic antireflux surgery, commonly referred to as laparoscopic Nissen fundoplication. While this surgery has long proven to be effective in treating the disease, the procedure is invasive and potential side effects of the fundoplication procedure may compromise otherwise excellent postsurgical results. A transoral incisionless fundoplication procedure using the EsophyX system with SerosaFuse fasteners was developed to mimic antireflux surgery, as a minimally invasive alternative procedure with potentially fewer side effects.