BACKGROUND: With the implementation of a new rotavirus immunization program in the United States in 2006, determining the potential health benefits of rotavirus vaccination is important. We estimated the burden of acute gastroenteritis hospitalizations and emergency department visits in US children that are potentially preventable by rotavirus vaccination. METHODS: We conducted a retrospective cohort analysis of children who in 1998-1999 were eligible to receive a now-withdrawn rotavirus vaccine (RotaShield) and were continuously enrolled in 1 of 6 managed care organizations in the Vaccine Safety Datalink. Estimates of vaccine effectiveness against all-cause gastroenteritis hospitalizations and emergency department visits adjusted according to month of birth, gender, and managed care organizations were calculated as 1 minus the risk ratio of outcomes among children in different dose groups. The burden of acute gastroenteritis prevented by vaccination was compared with the rotavirus burden estimated by 2 previously used indirect methods. RESULTS: The effectiveness of a full 3-dose RotaShield series over a 1-year follow-up period was 83% against all-cause gastroenteritis hospitalizations and 43% against all-cause gastroenteritis emergency department visits. An increasing number of doses improved the effectiveness in preventing gastroenteritis hospitalizations, but no clear trend was observed between number of doses and effectiveness in prevention of gastroenteritis emergency department visits. The proportion of gastroenteritis hospitalizations and emergency department visits prevented by vaccination was substantially greater than the 48% to 53% of year-round hospitalizations and 33% of emergency department visits estimated to result from rotavirus by indirect methods. CONCLUSIONS: The withdrawn rotavirus vaccine was highly effective in preventing hospitalizations and emergency department visits for all-cause acute gastroenteritis and the health benefits of vaccination against rotavirus may be greater than previously estimated.