It is critical to understand, analyze and improve the work system of medical residents in order to support the care processes in which they are involved, as well as their educational processes. The discipline of human factors (or ergonomics) (HFE) provides systems concepts and methods to improve the multi-faceted work system of medical residents and, therefore, care processes and educational processes, and outcomes for both patients and residents. In this chapter, we apply the SEIPS (Systems Engineering Initiative for Patient Safety) model to the work system of residents, and use it to explain how the outcomes of patient safety and medical resident well-being are related. Various challenges need to be addressed in order to improve residents’ work system. In particular, it is critical to adopt a systems approach that can optimize multiple outcomes for a range of stakeholders. In line with the participatory ergonomics approach, we contend that residents have a critical role to play in improving their work system; we describe various ways that this can be accomplished.