OBJECTIVES: To evaluate clinical practice patterns and patient outcomes among febrile low-risk infants with respiratory syncytial virus (RSV) infection or enterovirus (EV) meningitis after implementing a clinical practice guideline (CPG) that provides recommendations for managing febrile infants with RSV infection and EV meningitis. METHODS: Our institution implemented a CPG for febrile infants, which gives explicit recommendations for managing both RSV-positive and EV-positive infants in 2011. We retrospectively analyzed medical records of febrile infants ≤60 days old from June 2008 to January 2013. Among 134 low-risk RSV-positive infants, we compared the proportion of infants who underwent lumbar puncture (LP), the proportion of infants who received antibiotics, antibiotic hours of therapy (HOT), and length of stay (LOS) pre- and post-CPG implementation. Among 274 low-risk infants with EV meningitis, we compared HOT and LOS pre- and post-CPG implementation. RESULTS: Among low-risk RSV-positive patients, the proportion of infants undergoing LP, the proportion of infants receiving antibiotics, HOT, and LOS were unchanged post-CPG. Among low-risk infants with EV meningitis, HOT (79 hours pre-CPG implementation versus 46 hours post-CPG implementation, P < .001) and LOS (47 hours pre-CPG implementation versus 43 hours post-CPG implementation, P 5 .01) both decreased post-CPG. CONCLUSIONS: CPG implementation is associated with decreased antibiotic exposure and hospital LOS among low-risk infants with EV meningitis; however, there were no associated changes in the proportion of infants undergoing LP, antibiotic exposure, or LOS among low-risk infants with RSV. Further studies are needed to determine specific barriers and facilitators to effectively incorporate diagnostic viral testing into medical decision-making for these infants.