In this chapter, we present a research project entitled “Examining the Relationship Between Health IT and Ambulatory Care Workflow Redesign,” funded by the U.S. Agency for Healthcare Research and Quality (AHRQ). The project aimed to use rigorous and scientifically validated research methods to develop an enhanced understanding of (1) the causal relationship between health information technology (IT) implementation and ambulatory care workflow redesign; (2) sociotechnical factors and the role they play in mitigating or augmenting health IT’s impacts on workflow; and (3) the workflow impacts of health IT magnified through frequently occurring disruptive events such as interruptions and exceptions. The empirical study was conducted across six ambulatory care practices from two participating healthcare organizations in the U.S. It employed a prospective observational design with multiple data collection points before, during, and after various health IT implementations that took place during the project period at the two participating healthcare organizations. Research data were collected using a mixed methods approach consisting of ethnographic observations, time and motion observations, log analysis, semi-structured interviews, and member checking focus groups. A total of 120 clinicians and clinic staff participated in the study. The results show that a number of work and workflow processes were altered after the health IT implementations. These included a redistribution of clinicians’ and clinic staff’s time on different clinical tasks, repurposed usage of workspace, and increased level of interruptions, multitasking, and off-hours work activities. A majority of these changes appeared to be attributable to two interrelated causes: increased structured documentation requirements and shifted responsibilities among individuals serving different clinical roles.