We used the Pediatric Health Information System to examine annual trends in antiviral prescribing for hospitalized children with influenza before and during the 2009 H1N1 epidemic. During the 2009 H1N1 epidemic, the Centers for Disease Control and Prevention issued recommendations advising antiviral therapy for all hospitalized patients with influenza infection. Before the 2009 H1N1 outbreak, antivirals were prescribed for only 28% of hospitalized children with influenza. This increased sharply to 84% during the 2009 H1N1 period, indicating a favorable response by physicians to clinical guidelines.