Research knowledge translation into clinical practice pathways is a complex process that is often time-consuming and resource-intensive. Recent evidence suggests that the use of early goal-directed therapy (EGDT) in the emergency department care of patients with severe sepsis and septic shock results in a substantial mortality benefit; however, EGDT is a time- and resource-intensive intervention. The feasibility with which institutions may translate EGDT from a research protocol into routine clinical care, among settings with varying resources, staff, and training, is largely unknown. The authors report the individual experiences of EGDT protocol development, as well as preimplementation and postimplementation experiences, at three institutions with different emergency department, intensive care unit, and hospital organization schemes.