Purpose Neonatal herpes simplex virus (HSV) is relatively rare, but associated with high morbidity and mortality. Early recognition and treatment with acyclovir leads to better outcomes. HSV infections present a difficult clinical situation as there are no combinations of presenting signs and symptoms that can reliably identify all neonates with HSV. The purpose of this project was to standardize our institution’s practice, and improve education and confidence around HSV testing and treatment. Methods We instituted a QI initiative to implement HSV testing and treatment guidelines based on consensus between our ID, emergency medicine and hospitalist divisions. Guidelines included empiric testing with CSF and blood PCR and acyclovir treatment for all febrile neonates 21 days. Educational conferences were held with each division and the residents. An EMR clinical algorithm for febrile neonates was instituted. Surveys were sent before and after pathway implementation to measure providers’ confidence in making treatment decisions and educating others about the subject. Implementation was Dec 2015 and a retrospective chart review of febrile neonates aged 0-21 days from Jan 2015 to Nov 2016 was done to determine rates of adherence to guidelines. Results There were a total of 84 respondents to the pre- survey and 56 respondents to the post survey. There were significant increases in residents’ confidence in their ability to decide on testing and treatment of HSV, as well as confidence in their ability to educate learners (table 1). Residents’ confidence of two different attendings making the same decision (inter-provider reliability) remained unchanged. Attendings had a positive trend in their confidence to decide and educate that were not statistically significant, while inter-provider reliability significantly increased (table 2). On chart review, a total of 70 patients were identified with guideline adherence being 29.7% prior to, and 51.4% after implementation (P= < 0.01). Conclusion Our project made progress in standardizing our institution’s practice in HSV testing and treatment with practice change sustained 1 year after implementation. Improvements in residents’ confidence in decision-making, ability to educate as well as improvement in inter-provider reliability illustrate the multiple benefits of QI projects aimed at practice standardization. Future initiatives may benefit from having defined educational objectives outlined at project conception.