The availability of a well-established immunization registry to provide vaccination information, a school-located vaccination campaign followed by continued 2009 influenza A (H1N1) (pH1N1) activity, and a requirement to report hospitalized influenza cases provided an opportunity to estimate vaccine effectiveness (VE) of an initial dose of pH1N1 monovalent vaccine in children aged 7 months-9 years. Seventy-eight case children and 729 date-of-birth- and zipcode-matched controls were studied. The VE of a single vaccine dose in preventing pH1N1 hospitalization ≥ 14 days after vaccination was 82% (95% confidence interval [CI], 0%-100%; P = .04) in children aged 3-9 years but was zero (-3%; 95% CI, <0%-75%) in children aged 7-35 months. These findings are consistent with those from prelicensure immunogenicity studies and have implications for interpretation of immunogenicity studies and setting priorities for vaccination of young children in future pandemics. Immunization registries can provide a simple, rapid assessment of VE to evaluate and inform vaccination policy.