The initial concept of delivering RF energy to the gastroesophageal junction for the treatment of GERD was based on the well-established safety profile and scientific clinical evidence supporting the effectiveness of this technology in other disease states. As described in this article, the Stretta procedure is an endoluminal procedure inducing collagen tissue contraction, remodeling, and modulation of the triggering threshold for transient LES relaxations. The preclinical experience with this device included feasibility studies to determine optimal treatment parameters and device design. This was followed by longitudinal animal studies to elucidate the mechanism of safety and effect of this intervention as it relates to LES physiology and histopathology. In these studies, RF elevated the LES pressure and gastric yield pressure in a porcine model of botulinum toxin induced LES hypotension. The elevation in GYP more than 6 months was confirmed in a subsequent evaluation. Thickening of the LES after RF delivery has been demonstrated using histopathological evaluation and EUS. Additionally, using a canine model of triggered transient LES relaxations (tLESR), RF significantly reduced the frequency of tLESRs and reflux events. Additional evaluation was performed in human subjects undergoing esophagectomy, confirming feasibility and Histopathologic results of the treatment. Subsequent clinical trials confirm the safety and mechanism of action data of these pre-clinical studies and are presented in this publication.