The objective of this study was to estimate the rate and describe the epidemiology of necrotising enterocolitis (NEC) among neonates (infants <1 month of age) hospitalised in the United States. Hospital discharge records for neonates with an NEC diagnosis and an in-hospital death or routine discharge were selected for analysis from the 2000 Kids' Inpatient Database. An estimated 4463 (SE = 219) hospitalisations associated with NEC occurred among neonates in the United States during the year 2000, resulting in a hospitalisation rate of 109.9 [95% CI 97.2, 122.6] per 100 000 livebirths. The rate of NEC hospitalisations was highest among non-Hispanic Black neonates. The median hospital length of stay was 49 days. The in-hospital fatality rate was 15.2% (SE = 1.0%). Neonates who underwent a surgical procedure during hospitalisation were more likely to have a longer length of stay and to die than were those who did not have surgical intervention. Low-birthweight (LBW) neonates with NEC were more likely than LBW neonates hospitalised with other diagnoses to be very LBW (VLBW), non-Hispanic Black and male. In addition, compared with LBW neonates hospitalised with other diagnoses, LBW neonates with NEC had higher hospital charges and longer lengths of stay, and were more likely to die during hospitalisation. This study provides the first national estimate of the rate of hospitalisation for NEC among neonates in the United States. During 2000, there was one NEC hospitalisation per 1000 livebirths, with approximately 1 in 7 NEC hospitalisations ending in death. NEC accounts for substantial morbidity; thus, the development of prevention strategies and effective therapies continues to be an important issue.