BACKGROUND: Rotavirus causes approximately one-third to one-half (55,000-70,000 hospitalizations per year) of hospitalizations for acute gastroenteritis (AGE) among US children <5 years of age. We forecasted the potential reduction in the number of hospitalizations for rotavirus disease and AGE in US children during 2006-2015 as a result of the new rotavirus vaccine introduced in 2006. METHODS: The mean number of hospitalizations for AGE by calendar month among US children was determined using the National Hospital Discharge Survey from the period 1993-2005. From these baseline prevaccine estimates, we forecasted the effect of vaccine in reducing the number of hospitalizations for rotavirus disease and AGE during 2006-2015 with use of estimates of vaccine effectiveness and uptake. RESULTS: During 2006-2015, approximately 313,000 (45%) of an estimated 703,190 hospitalizations for rotavirus disease would be directly prevented by vaccination. A significant reduction in the number of hospitalizations for AGE should be detectable among infants aged 0-11 months during the first quarter of 2009, followed by children aged 12-23 months during 2010, and all children <5 years of age during 2011. CONCLUSIONS: Vaccination is expected to substantially reduce the health burden of hospitalizations for rotavirus disease among US children during 2006-2015, and the impact of vaccination based on direct protective effects alone was expected to first occur for hospitalizations for AGE among infants during winter 2009.