The 2009 pandemic influenza A (H1N1) (pH1N1) virus emerged in the United States in April 2009 (1) and has since caused significant morbidity and mortality worldwide (2-6). We compared pandemic influenza A (H1N1) (pH1N1)-associated deaths occurring from 15 April 2009 through 23 January 2010 with seasonal influenza-associated deaths occurring from 1 October 2007 through 14 April 2009, a period during which data collected were most comparable. Among 317 children who died of pH1N1-associated illness, 301 (95%) had a reported medical history. Of those 301, 205 (68%) had a medical condition associated with an increased risk of severe illness from influenza. Children who died of pH1N1-associated illness had a higher median age (9.4 vs 6.2 years; P<.01) and longer time from onset of symptoms to death (7 vs 5 days, P<.01) compared with children who died of seasonal influenza-associated illness. The majority of pediatric deaths from pH1N1 were in older children with high-risk medical conditions. Vaccination continues to be critical for all children, especially those at increased risk of influenza-related complications.