OBJECTIVE To determine whether the use of enhanced isolation precautions (droplet and contact precautions) for inpatients with respiratory tract viral infections is associated with a reduction in rate of nosocomial viral respiratory infections. DESIGN Quasi-experimental study with the rate of nosocomial respiratory virus infection as the primary dependent variable and rate of nosocomial Clostridium difficile infection as a nonequivalent dependent variable comparator. SETTING Cohen Children's Medical Center of NY, a tertiary-care children's hospital attached to a large general hospital. INTERVENTION During years 1 and 2 (July 2012 through June 2014), the Centers for Disease Control and Prevention/Healthcare Infection Control Practices Advisory Committee's recommended isolation precautions for inpatients with selected respiratory virus infections were in effect. Enhanced isolation precautions were in effect during years 3 and 4 (July, 2014 through June, 2016), except for influenza, for which enhanced precautions were in effect during year 4 only. RESULTS During the period of enhanced isolation precautions, the rate of nosocomial respiratory virus infections with any of 4 virus categories decreased 39% from 0.827 per 1,000 hospital days prior to enhanced precautions to 0.508 per 1,000 hospital days (P<.0013). Excluding rhinovirus/enterovirus infections, the rates decreased 58% from 0.317 per 1,000 hospital days to 0.134 per 1,000 hospital days during enhanced precautions (P<.0014). During these periods, no significant change was detected in the rate of nosocomial C. difficile infection. CONCLUSIONS Enhanced isolation precautions for inpatients with respiratory virus infections were associated with a reduction in the rate of nosocomial respiratory virus infections. Infect Control Hosp Epidemiol 2018;1-5.