We describe a novel approach to the study and prediction of technology-induced error in healthcare. The objective of our approach is to identify and reduce the potential for error so that the benefits of introducing information technology, such as Computerized Physician Order Entry (CPOE) or Electronic Health Records (EHRs), are maximized. The approach involves four phases. In Phase 1, we typically conduct small scale clinical simulations to assess whether or not the use of a new information technology can introduce error. (Human subjects are involved and user-system interactions are recorded.) In Phase 2, we analyze the results from Phase 1 to identify statistically significant relationships between usability issues and the occurrence of error (e.g., medication error). In Phase 3, we enter the results from Phase 2 into computer-based simulation models to explore the potential impact of the technology over time and across user populations. In Phase 4, we conduct naturalistic studies to examine whether or not the predictions made in Phases 2 and 3 apply to the real world. In closing, we discuss how the approach can be used to increase the safety of health information systems.