Objective To examine temporal trends in the US incidence of childhood asthma hospitalizations, in-hospital mortality, mechanical ventilation use, and hospital charges between 2000 and 2009. Study design This was a serial, cross-sectional analysis of a nationally representative sample of children hospitalized with acute asthma. The Kids Inpatient Database was used to identify children aged <18 years with asthma by International Classification of Diseases, Ninth Revision, Clinical Modification code 493.xx. Outcome measures were asthma hospitalization incidence, in-hospital mortality, mechanical ventilation use, and hospital charges. We examined temporal trends of each outcome, accounting for sampling weights. Hospital charges were adjusted for inflation to 2009 US dollars. Results The 4 separate years (2000, 2003, 2006, and 2009) of national discharge data included a total of 592 805 weighted discharges with asthma. Between 2000 and 2009, the rate of asthma hospitalization in US children decreased from 21.1 to 18.4 per 10 000 person-years (13% decrease; P-trend < .001). Mortality declined significantly after adjusting for confounders (OR for comparison of 2009 with 2000, 0.37; 95% CI, 0.17-0.79). In contrast, there was an increase in the use of mechanical ventilation (from 0.8% to 1.0%, a 28% increase; P-trend < .001). Nationwide hospital charges also increased from $1.27 billion to $1.59 billion (26% increase; P-trend < .001); this increase was driven by a rise in the geometric mean of hospital charges per discharge, from $5940 to $8410 (42% increase; P-trend <. 001). Conclusion Between 2000 and 2009, we found significant declines in asthma hospitalization and in-hospital mortality among US children. In contrast, mechanical ventilation use and hospital charges for asthma increased significantly over this same period.