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Seasonal Effectiveness of Live Attenuated and Inactivated Influenza Vaccine. BACKGROUND: Few observational studies have evaluated the relative effectiveness of live attenuated (LAIV) and inactivated (IIV) influenza vaccines against medically attended laboratory-confirmed influenza. METHODS: We analyzed US Influenza Vaccine Effectiveness Network data from participants aged 2 to 17 years during 4 seasons (2010-2011 through 2013-2014) to compare relative effectiveness of LAIV and IIV against influenza-associated illness. Vaccine receipt was confirmed via provider/electronic medical records or immunization registry. We calculated the ratio (odds) of influenza-positive to influenza-negative participants among those age-appropriately vaccinated with either LAIV or IIV for the corresponding season. We examined relative effectiveness of LAIV and IIV by using adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression. RESULTS: Of 6819 participants aged 2 to 17 years, 2703 were age-appropriately vaccinated with LAIV (n = 637) or IIV (n = 2066). Odds of influenza were similar for LAIV and IIV recipients during 3 seasons (2010-2011 through 2012-2013). In 2013-2014, odds of influenza were significantly higher among LAIV recipients compared with IIV recipients 2 to 8 years old (OR 5.36; 95% CI, 2.37 to 12.13). Participants vaccinated with LAIV or IIV had similar odds of illness associated with influenza A/H3N2 or B. LAIV recipients had greater odds of illness due to influenza A/H1N1pdm09 in 2010-2011 and 2013-2014. CONCLUSIONS: We observed lower effectiveness of LAIV compared with IIV against influenza A/H1N1pdm09 but not A(H3N2) or B among children and adolescents, suggesting poor performance related to the LAIV A/H1N1pdm09 viral construct.