OBJECTIVE: To compare inpatient resource use trends for healthy children and children with chronic health conditions of varying degrees of medical complexity. DESIGN: Retrospective cohort analysis. SETTING: Twenty-eight US children's hospitals. PATIENTS: A total of 1 526 051 unique patients hospitalized from January 1, 2004, through December 31, 2009, who were assigned to 1 of 5 chronic condition groups using 3M's Clinical Risk Group software. INTERVENTION: None. MAIN OUTCOME MEASURES: Trends in the number of patients, hospitalizations, hospital days, and charges analyzed with linear regression. RESULTS: Between 2004 and 2009, hospitals experienced a greater increase in the number of children hospitalized with vs without a chronic condition (19.2% vs 13.7% cumulative increase, P .001). The greatest cumulative increase (32.5%) was attributable to children with a significant chronic condition affecting 2 or more body systems, who accounted for 19.2% (n = 63 203) of patients, 27.2% (n = 111 685) of hospital discharges, 48.9% (n = 1.1 million) of hospital days, and 53.2% ($9.2 billion) of hospital charges in 2009. These children had a higher percentage of Medicaid use (56.5% vs 49.7%; P .001) compared with children without a chronic condition. Cerebral palsy (9179 [14.6%]) and asthma (13 708 [21.8%]) were the most common primary diagnosis and comorbidity, respectively, observed among these patients. CONCLUSIONS: Patients with a chronic condition increasingly used more resources in a group of children's hospitals than patients without a chronic condition. The greatest growth was observed in hospitalized children with chronic conditions affecting 2 or more body systems. Children's hospitals must ensure that their inpatient care systems and payment structures are equipped to meet the protean needs of this important population of children.