OBJECTIVE To identify barriers to implementation of a written protocol for early goal-directed therapy for severe sepsis in the busiest emergency departments in the United States. METHODS Telephone survey with both quantitative and qualitative analysis. METHODS Two busiest teaching and two busiest nonteaching emergency departments in each of the 25 most densely populated combined statistical areas in the United States. METHODS Twenty-four physician directors and 40 nursing managers representing 53% of the 100 emergency departments surveyed. METHODS Survey questionnaire. RESULTS Respondents identified lack of available nursing staff to perform the procedure, the inability to monitor central venous pressure in the emergency department, and challenges in identifying septic patients as the most frequent barriers. Although nurse managers and physicians identified similar barriers, nurses were more likely than physicians to list central venous catheter insertion as an important barrier (38% vs. 5%; p = .01), and physicians were more likely to endorse lack of agreement with the early goal-directed therapy resuscitation protocol (16% vs. 0%; p = .03). There were no statistically significant differences in the rankings assigned by clinicians from teaching and nonteaching hospitals. Qualitative analysis of open-ended questions identified barriers in a number of areas, including barriers to initiating the protocol process and factors that distinguish sepsis from other time-sensitive diseases in the emergency department. CONCLUSIONS Nurse managers and physician directors of busy emergency departments representing the largest urban areas in the United States identify multiple barriers to implementing time-sensitive resuscitation to patients with severe sepsis. More than half of all respondents recognized a critical shortage of nursing staff, problems in obtaining central venous pressure monitoring, and challenges in identification of patients with sepsis as the largest roadblocks to overcome in implementing early goal-directed therapy.