BACKGROUND AND PURPOSE: Health economic analyses seek to assess the relative value (cost vs health benefit trade-offs) of medical technologies. However, these methods have been underused in studies of the electrocardiogram (ECG). METHODS: We develop a framework for the economic evaluation of the ECG as a decision support tool within broader treatment strategies. We then apply this framework to the development of an economic study protocol for the Prehospital Wireless Transmission of Electrocardiograms to a Cardiologist via a Hand-held Device Multicenter study. RESULTS: Our framework defines key cost-effectiveness concepts and describes alternative methods for estimating medical costs and health benefits. We demonstrate how this framework has been applied to develop the Prehospital Wireless Transmission of Electrocardiograms to a Cardiologist via a Hand-held Device Multicenter economic protocol. CONCLUSIONS: The conduct of health economic studies alongside ECG clinical studies could provide important information for those seeking to promote newer ECG applications that require significant financial investments.