Background: University Hospitals (UHs) are key players in contributing to a sustainable health care system. In the Netherlands the eight UHs joined forces from 2016 till 2018 within the Citrien fund (CF) – program eHealth to develop sustainable eHealth solutions by carrying out 32 research projects. Objective: The objective of this study was to develop an evaluation study protocol that would be capable of evaluating the first Dutch University Hospitals eHealth program in depth. Methods: To develop the protocol three consecutive steps were carried out: 1) a rapid review to find suitable eHealth evaluation frameworks and eHealth project progress indicators, 2) assessment of the selected eHealth evaluation frameworks to determine the most suitable framework to evaluate CF - program eHealth, and 3) development of a mixed-methods study to evaluate eHealth project progress indicators in relation to the 32 eHealth research projects. Results: The ‘Commonwealth Scientific and Industrial Research Organization (CSIRO) framework for evaluating telehealth trials or programs’ was deemed most suitable for evaluating CF - program eHealth. The aspects planning, needs assessment, policy/organization, technology, ethics, legal, and finance, were considered useful indicators for monitoring the progress of an eHealth project, and therefore incorporated into the survey. Conclusion: The developed evaluation study protocol will be used to evaluate the first Dutch University Hospitals’ eHealth program, the CF – program eHealth, and therewith contribute to maximizing successful uptake of eHealth solutions. Also, the selected set of eHealth project performance indicators could be used by researchers or policymakers to securely monitor the progress of eHealth projects.