BACKGROUND AND OBJECTIVE: Rotavirus vaccination is discouraged during hospitalization given concerns regarding live attenuated virus transmission, although recommended upon discharge. Infants should have vaccination initiated by 104 days of age or they become age-ineligible. Our institution believed the known risk of severe disease in unvaccinated infants outweighed the theoretical risk of transmission. We routinely administer RotaTeq (RV5) to age-eligible hospitalized infants on enteral feeds. The objective of this study was to determine the safety of RV5 vaccination among vaccinated (VI) and unvaccinated infants (UVI) within the NICU. METHODS: A retrospective review identified VI between 2008 and 2010, and UVI geographically located near VI within 15 days of vaccination. We screened for gastrointestinal symptoms among UVI by using an electronic medical record query (trigger tool) to identify infants with orders for bowel rest, abdominal imaging, and antibiotics. Trigger-positive infants had full chart review. RESULTS: Most VI (76%) were either asymptomatic (25% [24 of 96]) or symptomatic but unchanged from baseline (51% [49 of 96]) postvaccination. Although 24% of VI had clinical status changes postvaccination, none were directly attributed to RV5. Among 801 neighboring UVI, 10 (1.2%) had clinical status changes, none directly attributed to RV5, but mostly bacterial sepsis or preexisting gastrointestinal pathology. Two UVI underwent stool analysis; both negative for rotavirus. CONCLUSIONS: RV5 was well tolerated in hospitalized infants, with most postvaccination symptoms attributed to preexisting symptoms. UVI seemed to have a low risk of symptomatic transmission. Inpatient administration ensures that age-eligible infants are vaccinated regardless of hospital duration. Prospective evaluation of safety and transmissibility is needed.