Background: Febrile neutropenia (FN) is a common complication in oncology patients and is associated with significant morbidity and mortality if untreated. Because of this, it is regarded as a medical emergency. FN treatment guidelines universally recommend the prompt initiation ( < 60 minutes) of intravenous antibiotic therapy. We hypothesized that a quality initiative project creating a new FN clinical practice guideline (CPG) would reduce the time to antibiotic administration (TTA) for inpatient oncology patients with FN. Methods: This prospective study compared patients diagnosed with an initial episode of FN (4/2015-8/2015) with historical controls (4/2013-8/2013) on an inpatient oncology floor at a tertiary care academic hospital. Interventions included the development of an institutional CPG which standardized the definition of FN, implementation of a new clinical workflow, creation of education sessions for LIP’s and RN’s, and creation of an electronic FN order set. The primary outcome was TTA, with target goal being < 60 minutes from the onset of fever. Secondary outcomes included time to antibiotic order, need for ICU care, and 30-day mortality. P-values were calculated using a chi-square test. Results: In total, 31 consecutive FN episodes were observed over the 5-month study period. The median TTA decreased from 112 minutes in 2013 to 37.5 minutes in 2015 (p < 0.001). 30/31 (97%) patients in the 2015 group had their antibiotics ordered within 60 minutes vs 14/22 (64%) in 2013 (p = 0.002). 26/31 (84%) patients in the 2015 group had antibiotics administered within 60 minutes vs 4/22 (18%) in 2013 (p < 0.001). There was no significant difference in need for ICU care (16% in 2015 vs 9% in 2013, p = NS) or 30-day mortality (6% in 2015 vs 5% in 2013, p = NS). Conclusions: The inpatient FN CPG is a significant quality improvement initiative that has shown significant improvements in TTA. We were able to demonstrate value by a significant decrease in median TTA compared to historical controls with a significantly increased percentage of patients having both antibiotics ordered and administered within 60 minutes. In our cohort of patients, no significant differences were noted in rates of ICU care or 30-day mortality.