Background: The A(H1N1)pdm09 virus strain used in the live attenuated influenza vaccine was changed for the 2015-2016 influenza season because of its lack of effectiveness in young children in 2013-2014. The Influenza Vaccine Effectiveness Network evaluated the effect of this change as part of its estimates of influenza vaccine effectiveness in 2015-2016.Methods: We enrolled patients 6 months of age or older who presented with acute respiratory illness at ambulatory care clinics in geographically diverse U.S. sites. Using a test-negative design, we estimated vaccine effectiveness as (1-OR)×100, in which OR is the odds ratio for testing positive for influenza virus among vaccinated versus unvaccinated participants. Separate estimates were calculated for the inactivated vaccines and the live attenuated vaccine.Results: Among 6879 eligible participants, 1309 (19%) tested positive for influenza virus, predominantly for A(H1N1)pdm09 (11%) and influenza B (7%). The effectiveness of the influenza vaccine against any influenza illness was 48% (95% confidence interval [CI], 41 to 55; P<0.001). Among children 2 to 17 years of age, the inactivated influenza vaccine was 60% effective (95% CI, 47 to 70; P<0.001), and the live attenuated vaccine was not observed to be effective (vaccine effectiveness, 5%; 95% CI, -47 to 39; P=0.80). Vaccine effectiveness against A(H1N1)pdm09 among children was 63% (95% CI, 45 to 75; P<0.001) for the inactivated vaccine, as compared with -19% (95% CI, -113 to 33; P=0.55) for the live attenuated vaccine.Conclusions: Influenza vaccines reduced the risk of influenza illness in 2015-2016. However, the live attenuated vaccine was found to be ineffective among children in a year with substantial inactivated vaccine effectiveness. Because the 2016-2017 A(H1N1)pdm09 strain used in the live attenuated vaccine was unchanged from 2015-2016, the Advisory Committee on Immunization Practices made an interim recommendation not to use the live attenuated influenza vaccine for the 2016-2017 influenza season. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health.). [ABSTRACT FROM AUTHOR]