BACKGROUND: Children with multiple chronic conditions (CMCC) are increasingly using hospital care. We assessed how much of US pediatric inpatient care is used by CMCC and which chronic conditions are the key drivers of hospital use. METHODS: A retrospective analysis of all 2.3 million US acute-care hospital discharges in 2012 for children age 0 to 18 years in the Kids' Inpatient Database. The approximately 4.5 million US hospitalizations for pregnancy, childbirth, and newborn and neonatal care were not assessed. We adapted the Agency for Healthcare Research and Quality's Chronic Condition Indicators to classify hospitalizations for children with no, 1, or multiple chronic conditions, and to determine which specific chronic conditions of CMCC are associated with high hospital resource use. RESULTS: Of all pediatric acute-care hospitalizations, 34.3% were of children with no chronic conditions, 36.5% were of those with 1 condition, and 29.3% were of CMCC. Of the $23.6 billion in total hospital costs, 19.7%, 27.4%, and 53.9% were for children with 0, 1, and multiple conditions, respectively, and similar proportions were observed for hospital days. The three populations accounted for the most hospital days were as follows: children with no chronic condition (20.9%), children with a mental health condition and at least 1 additional chronic condition (20.2%), and children with a mental health condition without an additional chronic condition (13.3%). The most common mental health conditions were substance abuse disorders and depression. CONCLUSIONS: CMCC accounted for over one-fourth of acute-care hospitalizations and one-half of all hospital dollars for US pediatric care in 2012. Substantial CMCC hospital resource use involves children with mental health-related conditions.