Background: Although individuals with Down syndrome are increasingly living into the adult years, infants and young children with the syndrome continue to be at increased risk for health problems. Using linked, statewide administrative hospital discharge records of all infants with Down syndrome born over a 3-year period, this study "follows forward" over 200 infants with Down syndrome from each individual's birth until they turn 3 years of age. By utilizing this procedure, we were able to assess the amount, reasons for, and timing of inpatient hospitalization and to investigate how congenital heart defects (CHDs) relate to hospitalization for young children with Down syndrome. Method: This population-based, retrospective study used statewide administrative hospital discharge data. Subject inclusion criteria included residents of Tennessee, born between 1997 and 1999, and diagnosed with Down syndrome at birth. Inpatient records were linked to create person-record histories of hospitalization from birth to age 3. Main outcomes included the number of Non-birth Hospitalizations, length of stay, principal and other diagnosis codes to indicate reason(s) for hospitalization, and patient's age at first (non-birth) hospitalization. Procedure codes were added to determine if children with CHD were hospitalized primarily for operations on the heart. Results: Of 217 births, 213 children survived birth; 54% (115) had CHDs. Almost half (49.8%) of all children were hospitalized before age 3; these 106 children were admitted 245 times. Children with CHDs were 2.31 times more likely to be hospitalized than children without CHDs. Respiratory illnesses affected 64.9% of all hospitalized children with CHD, were the principal diagnoses in 38.3% of their hospitalizations, and were the main principal diagnoses for non-CHD children. Thirty-three (of 77) hospitalized children with CHD underwent cardiac surgeries, accounting for 19.3% of all admissions. Median time to first hospitalizationwas 96 days (CI: 78-114) for CHD infants, 197 days (CI: 46-347) for non-CHD infants. Conclusions: Children with Down syndrome are at high risk for early hospitalization. Prevention and treatment of respiratory illnesses require more attention. Down syndrome is associated with early, serious, physical health problems and substantial inpatient care use.