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BackgroundSustainable implementation of telemonitoring in health care is challenging, especially if one aims to scale up telemonitoring initiatives nationwide. The National collaborative eHealth program in the Netherlands is supporting the nationwide upscaling of telemonitoring in 3 clinical domains by implementing telemonitoring in all Dutch university medical centers (UMCs). The chosen telemonitoring concepts are (1) telemonitoring solutions in the domain of cardiology, (2) telemonitoring solutions providing care from a distance in obstetrics, and (3) telemonitoring solutions monitoring vital functions in hospital wards. ObjectiveThe aim of this study is to evaluate the upscaling of telemonitoring in Dutch university hospitals in order to gain a better knowledge of the process, methods, and outcomes of nationwide upscaling strategies. Our hypothesis is that by the completion of the Citrien program’s scale-up, telemonitoring will be operational in all UMCs but not normalized in routine care. MethodsA before-and-after study will be conducted to assess upscaling. The theoretical frameworks used are the framework for nonadoption, abandonment, scale-up, spread, and sustainability; the Normalization Process Theory; and a project management tool Project Canvas. The primary outcome of the study is the degree of normalization to which health care providers at UMCs consider telemonitoring a part of their routine practice, measured using the Normalization MeAsurement Development tool (NoMAD). Our secondary outcome is the uptake of telemonitoring at the Dutch UMCs, using management data from UMCs’ business intelligence systems query. ResultsData will be collected between May 2020 and December 2022. Results were retrieved in June 2023. UMCs’ business intelligence systems are queried for data for the secondary outcome measures. There is a risk that the UMCs will not be able to provide this management information. The laws and regulations governing telemonitoring in the Netherlands are changing, with the Electronic Data Exchange in Health Care Act (Wet elektronische gegevensuitwisseling in de zorg) and the European Health Data Space Act expected to positively influence implementation and upscaling. ConclusionsThe Citrien program is a nationally coordinated change management program that is scaling up telemonitoring across contexts and settings. This study will produce original data on the uptake and upscaling of telemonitoring at Dutch UMCs. Future initiatives to implement eHealth in the health care sector may be guided by the wide range of success factors, obstacles, and experiences collected through this program. The network itself may be of great value impacting future acceleration of eHealth initiatives. International Registered Report Identifier (IRRID)DERR1-10.2196/45201