Background: Febrile neutropenia in immunocompromised children is a medical emergency and requires prompt administration of antibiotics and supportive care management to prevent death from sepsis. We have previously shown that improvement in time to antibiotic administration from a baseline of 108 minutes was decreased to 64 minutes in 67 children in six St. Jude affiliate clinics. The improvement was achieved by designing a unique order set and process for prompt dispensing of antibiotics at each affiliate site. However, the clinical assessment of patients after antibiotic administration to provide early intervention for treatment of septic shock did not improve. Management of fluid status, oxygen therapy, and blood pressure support are critical for optimal outcome. The time from antibiotic administration to clinical assessment remained above the expected time of 15 minutes at an average of 60 minutes. To improve the post-antibiotic management, additional guidelines were established and monitored for compliance. Methods: Clinical guidelines were written. The guidelines included: patient assessed by nurse and vital signs checked within 15 minutes of arrival, patient assessed by a clinician within 30 minutes of arrival, antibiotic administrated within 60 minutes of arrival, nurse completed post-antibiotic assessment and vital signs rechecked within 15 minutes of administration, and clinician completed post antibiotic assessment within 30 minutes of administration. Results: After establishing guidelines, each site developed a process for implementation using a similar approach of automated order sets, time reminders, and staff education of the initial management of septic shock. Chart reviews were done at one year after implementation and all were in compliance. Conclusions: Clinical guidelines, automated order sets, and continued awareness and education in the management of immunocompromised children with febrile neutropenia improved compliance with this quality project. Continued monitoring is needed to ensure the results are sustained.