Health information technology (HIT) is intended to expedite clinical work and to reduce the frequency of preventable medical errors. However, after several decades, HIT is yet to reach its full potential. Usability problems and difficult interaction have been identified as key barriers to high quality performance. This work presents a multifaceted cognitive methodology, the Distributed Cognitive Resources (DCR) framework for the characterization of cognitive demand on users by complex clinical information systems. It was used to explain variation in user performance and the rate of cognitive error in a study of computer-based clinical ordering. Analyses suggested that the relative distribution of cognitive resources embodied in the clinical application placed extraneous cognitive demand on users. Results showed that human cognition is routinely distributed across technology and artifacts and that systems of greater interface complexity with poor usability characteristics require significant cognitive effort to operate. The methods within the DCR framework can suggest better interface design alternatives to developers of clinical information systems and may help to reduce error.