ABSTRACT The vagus nerve is involved in normal physiology, and disturbances in vagal control have been implicated in several pathophysiological conditions. However, there is a lack of information on the physiology of this nerve in humans as well as multi-organ responses to vagal nerve stimulation (VNS), despite over 100,000 VNS implants worldwide to treat epilepsy, depression, anxiety, and gastrointestinal disorders. Likewise, very little is known about how to best optimize VNS settings for existing therapies or how to develop VNS for new therapies. The proposed Research Evaluating Vagal Excitation and Anatomical Linkages (REVEAL) center aims to conduct groundbreaking research on the effect of VNS on four key autonomic systems: the autonomic nervous system (ANS), the cardiovascular system, the immune system, and metabolic system. The ambitious scope of the research requires the participation of eight major academic and medical institutions with over 40 participating key personnel, over 140 patients, an External Advisory Board (which includes patient advocates), a Data and Safety Monitoring Board, and an NIH Steering Committee and other NIH personnel. REVEAL will have three aims corresponding to its Cores. The Clinical Core will manage over 140 patients and clinical staff from 8 different institutions to obtain consistent data on VNS effects on ANS, the cardiovascular system, the immune system, and metabolism. The Data and Analysis Core will gather, store, and analyze data from clinical sites to produce publicly available datasets for development of VNS-based therapeutics and other research. The Administration Core will coordinate the work of the REVEAL Cores and stakeholders to meet the goals of NIH SPARC’s VESPA program.