This paper describes an approach to studying medical error and workflow that can be applied to help ensure the safety of new healthcare information systems. The approach focuses on identification of usability problems resulting from implementation of new information technology, as well as identification of problems related to changes in workflow. The paper illustrates how the approach can be applied in the simulation-based analyses of emerging healthcare information systems. The paper includes discussion of the application of an approach to identifying inadvertent changes in healthcare workflow that may result from design issues in a range of information technologies including medication order entry systems. General implications for the design, development and evaluation of safer healthcare information systems are discussed. It is argued that there is a need for thorough simulation-based testing of systems under a variety of conditions before they are released in order to ensure the safety of healthcare.