Background: Obtaining blood cultures prior to antibiotic administration in emergency department patients admitted with a diagnosis of sepsis has been considered standard of care and a cornerstone of the Surviving Sepsis guidelines. Several studies in other disease states, most notably pneumonia, have questioned the utility of this practice. Objectives: The objective of this study is to determine the impact and clinical relevance of routine blood cultures obtained in the ED for patients with the diagnosis of sepsis, severe sepsis, or septic shock. Methods: We performed a retrospective analysis of consecutive adult patients (age 18 and older) diagnosed and treated for sepsis in an urban, academic Emergency Department between 09/2014 - 02/2015. Inclusion criteria were admission through the Emergency Department and clinical diagnosis of sepsis with routine blood cultures obtained prior to initiation of antibiotics. Blood cultures were classified as positive, negative, or contaminant. Additionally, a physician reviewed individual charts for antimicrobial sensitivities, inpatient documentation, and timing of antibiotic therapy changes in correlation with true positive blood culture results. Results: There were 194 patients admitted through the ED with blood cultures obtained and meeting the above criteria. Of these, 45 of 194 patients (23.2%) had evidence of positive blood cultures, with 30 of the 45 positive blood cultures (15.4%) resulting in true bacteremia. Blood culture results altered antibiotic therapy in 15 patients (7.7%). Diagnoses included indwelling lines or hardware (5), pneumonia (4), complicated UTI (4), and 2 patients with possible endocarditis. For the other 15 patients with bacteremia whose therapy was not altered, cultures from other sources were positive during admission (urine, vaginal cultures, surgical cultures, etc). Conclusion: Blood cultures obtained in patients admitted with the diagnosis of sepsis from the ED altered antibiotic therapy in 7.7% of patients. Bacteremia secondary to indwelling catheters/devices and pneumonia patients on ICU status resulted in 60% of these cases. Additional studies are needed to further delineate which ED patients admitted with the diagnosis of sepsis would benefit from blood cultures.