Use of clinical simulation in the design and evaluation of eHealth systems and applications has increased during the last decade. This paper describes a methodological approach for using clinical simulations in the design and evaluation of clinical information systems. The method is based on experiences from more than 20 clinical simulation studies conducted at the ITX-lab in the Capital Region of Denmark during the last 5 years. A ten-step approach to conducting simulations is presented in this paper. To illustrate the approach, a clinical simulation study concerning implementation of Digital Clinical Practice Guidelines in a prototype planning and coordination module is presented. In the case study potential benefits were assessed in a full-scale simulation test including 18 health care professionals. The results showed that health care professionals can benefit from such a module. Unintended consequences concerning terminology and changes in the division of responsibility amongst healthcare professionals were also identified, and questions were raised concerning future workflow across sector borders. Furthermore unexpected new possible benefits concerning improved communication, content of information in discharge letters and quality management emerged during the testing. In addition new potential groups of users were identified. The case study is used to demonstrate the potential of using the clinical simulation approach described in the paper.