Abstract: Reliable, real-time heart and respiratory rates are key vital signs used in evaluating the physiological status in many clinical and non-clinical settings. Measuring these vital signs generally requires superficial attachment of physically or logistically obtrusive sensors to subjects that may result in skin irritation or adversely influence subject performance. Given the broad acceptance of ingestible electronics, the approach disclosed here enables vital sign monitoring internally from the gastrointestinal tract. The large animal (porcine) experiments and a robust processing disclosed herein demonstrate the feasibility of this approach. Implementing vital sign monitoring as a stand-alone technology or in conjunction with other ingestible devices has the capacity to significantly aid telemedicine, optimize performance monitoring of athletes, military service members, and first-responders, as well as provide a facile method for rapid clinical evaluation and triage.