Background - EsophyX™ is a novel endolumenal therapeutic option for treatment of gastroesophageal reflux disease (GERD). The device is passed over an endoscope into the stomach where it deploys a series of fasteners to create a neo-gastroesophageal valve. Phase I European data has demonstrated proton pump inhibitor (PPI) discontinuation in 80% of patients at six months. The objective of this study was to demonstrate the safety and characterize the effectiveness of this approach by measuring postprocedural subjective outcomes, such as quality of life and symptom severity.Methods - This is a retrospective multicenter study of consecutive patients with GERD having undergone endolumenal fundoplication with the EsophyX™ device, at two institutions. Demographic and periprocedural data were collected. At follow-up, PPI usage was elicited and two validated questionnaires were administered measuring GERD health related quality of life (HRQL) (range 0-50) and symptom severity (range 0-72). Data is reported as mean ± standard deviation.Results - Seven patients (3 males, 4 females) underwent endolumenal fundoplication between September and November 2007. Mean age was 50 ± 14 years and body mass index was 32 ± 4 kg/m2. All patients had abnormal pre-procedural ph studies. All cases were done under general anesthesia with nasotracheal intubation. Mean procedural time was 63 ± 28 minutes and there were no complications. At a mean follow-up of 39 ± 22 days, 4/7 patients were not taking PPIs. These patients reported being satisfied with their present condition, whereas those still on PPIs were either neutral or dissatisfied. Mean GERD-HRQL score was 8 ± 8 and mean symptom severity score was 18 ± 16. Conclusion - The initial North American experience with EsophyX™ endolumenal fundoplication suggests that this procedure is associated with low morbidity and is both safe and effective in treating GERD. Further studies comparing this technique to conventional medical and surgical therapies are necessary.