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We tested the hypothesis that the use of mechanical ventilator support in children hospitalized with influenza during the 2009 H1N1 influenza A (H1N1) pandemic was higher than would be expected in children hospitalized for seasonal influenza after adjusting for patient risk.Retrospective cohort study.Forty-three U.S. pediatric hospitals.Children <18 yrs old with a discharge diagnosis of influenza admitted July 2006 through March 2009 (seasonal influenza) and June through December 2009 (2009 pandemic influenza A).None.We included 10,173 children hospitalized with seasonal influenza and 9837 with presumed 2009 pandemic influenza A. The 2009 pandemic influenza A cohort was older (median 5.0 vs. 1.9 yrs), more likely to have asthma (30% vs. 18%), and less likely to receive mechanical ventilation (7.1% [n = 701] vs. 9.2% [n = 940]). Using logistic regression, we created a multivariable model of risk factors associated with endotracheal mechanical ventilator support in the seasonal influenza cohort and used this model to predict the number of expected mechanical ventilation cases in children with presumed 2009 pandemic influenza A. Adjusted for underlying health conditions, race, age, and a co-diagnosis of bacterial pneumonia, the observed/expected rate of mechanical ventilation in the presumed 2009 pandemic influenza A cohort was 0.74 (95% confidence interval 0.68–0.79). Early hospital treatment with influenza antiviral medications was associated with decreased initiation of mechanical ventilation on hospital day ≥3 in the seasonal influenza (odds ratio 0.66; 95% confidence interval 0.45–0.97) and 2009 pandemic influenza A (odds ratio 0.23; 95% confidence interval 0.16–0.34) periods; influenza antiviral use in the 2009 pandemic influenza A period was much higher (70% vs. 20%; p < .001).Although the number of children with a hospital discharge diagnosis of influenza almost tripled during the 2009 pandemic influenza A period, the risk-adjusted proportion of children receiving mechanical ventilation was lower than we would have predicted in a seasonal influenza cohort. Early hospital use of influenza antiviral medications was associated with a decrease in late-onset mechanical ventilation.