Background: Central line associated bloodstream infections are a common cause of bacteremia and sepsis in pediatric patients with intestinal failure, secondary to long-term CVC use. Methods: An IRB approved retrospective chart review was conducted on TPN-dependent patients with IF who had an identified CLABSI and presented to Children's of Alabama's emergency department (ED) and were admitted to the hospital. Results: Forty-four patients were included in the study, 28 in the first 18-month period and 26 in the second, with 10 in both populations. After implementation, mean time from ED presentation to antibiotic ordered and ED admission to antibiotic administered were lower. Mean time between antibiotic administration and admission to the floor was greater, and number of infectious disease consultations was greater. Floor-ICU transfers were lower, readmissions within 30 days was similar, and mean length of stay was similar. Conclusion: A collaborative, multidiscipline-supported protocol for the care of patients with IF presenting to the ED enhances efficiency of antibiotic ordering/administration, as well as reduces the number of unplanned floor-ICU transfers.