Recently a new rotavirus vaccine was licensed in the United States and recommended for universal immunization of American children. The impact of the vaccine on a decrease in hospitalizations will take several years to assess and will be based on the availability of good baseline data on the disease. We used the largest US hospital discharge database available, the Healthcare Cost and Utilization Project (HCUP), to study national rates, trends, and risk factors for diarrhea- and rotavirus-associated hospitalizations and deaths amongchildren <5 years of age, to establish a baseline against which vaccine implementation can be measured. Rotavirus remained the most important cause of pediatric diarrhea throughout the study period (1993–2003). When the data were extrapolated to the US population, rotavirus was estimated to be the cause of ∼60,000 hospitalizations and 37 deaths annually. Black infants had a significantly higher risk of being hospitalized with and dying from rotavirus disease early in life, compared with white infants (risk ratio [RR] for hospitalization by 12 months of age was 2.4, with a 95% confidence interval [CI] of 1.2–4.7; RR for death was 2.0, with a 95% CI of 1.7–2.5). Such racial differences in age and risk of rotavirus-associated hospitalization and death highlight the importance of timely and early rotavirus immunization of minority children. The HCUP database serves as a sensitive and robust data source for monitoring the impact of a rotavirus-immunization program in the United States.