The purpose of this study was to examine the effect of an Emergency Department (ED) protocol to reduce time to antibiotic administration in the febrile infant less than 3 months of age with a rectal temperature > or =38.0 degrees C. We conducted a before-after study of a febrile infant quality improvement initiative in an urban pediatric ED with approximately 35,000 patient visits per year. Records of infants less than 3 months of age presenting with a rectal temperature > or =38.0 degrees C, who underwent a full septic work-up (blood, urine, and cerebrospinal fluid studies, and possibly chest radiography), were identified by using daily ED logs. This review was performed in the month before and then 12 months after institution of the "Septic Infant Work-up Sheet" and a set of interventions (Febrile Infant Protocol) designed to streamline care of the febrile infant and to reduce the time to antibiotic administration. Data were analyzed by using the Kaplan-Meier survival estimate and the log-rank test. Patient demographic characteristics and severity of illness were similar across months; however, ED process of care was significantly changed. Initial analysis revealed a median time to antibiotics of 142 min. Subsequent analysis after implementation of the Febrile Infant Protocol revealed a median time to antibiotics of 105 min. This represents an overall time reduction of 25% from time of presentation to antibiotic administration. In conclusion, a guideline-based ED febrile infant protocol changed clinical practice and improved time to antibiotics.