BACKGROUND AND OBJECTIVES: Children who experience high health care costs are increasingly enrolled in clinical initiatives to improve their health and contain costs. Hospitalization is a significant cost driver. We describe hospitalization trends for children with highest annual inpatient cost (CHIC) and identify characteristics associated with persistently high inpatient costs in subsequent years. METHODS: Retrospective study of 265 869 children age 2 to 15 years with >/=1 admission in 2010 to 39 children's hospitals in the Pediatric Health Information System. CHIC were defined as the top 10% of total inpatient costs in 2010 (n = 26 574). Multivariate regression and regression tree modeling were used to distinguish individual characteristics and interactions of characteristics, respectively, associated with persistently high inpatient costs (>/=80th percentile in 2011 and/or 2012). RESULTS: The top 10% most expensive children (CHIC) constituted 56.9% ($2.4 billion) of total inpatient costs in 2010. Fifty-eight percent (n = 15 391) of CHIC had no inpatient costs in 2011 to 2012, and 27.0% (n = 7180) experienced persistently high inpatient cost. Respiratory chronic conditions (odds ratio [OR] = 3.0; 95% confidence interval [CI], 2.5-3.5), absence of surgery in 2010 (OR = 2.0; 95% CI, 1.8-2.1), and technological assistance (OR = 1.6; 95% CI, 1.5-1.7) were associated with persistently high inpatient cost. In regression tree modeling, the greatest likelihood of persistence (65.3%) was observed in CHIC with >/=3 hospitalizations in 2010 and a chronic respiratory condition. CONCLUSIONS: Most children with high children's hospital inpatient costs in 1 year do not experience hospitalization in subsequent years. Interactions of hospital use and clinical characteristics may be helpful to determine which children will continue to experience high inpatient costs over time.