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Introduction: Influenza causes significant morbidity among young children, and vaccination remains the best strategy to prevent disease. Understanding factors influencing early influenza vaccination uptake are important to identify strategies to increase vaccination rates., Objective: To assess maternal and neonatal factors associated with influenza vaccination among first-born children within the first two years of life., Methods: We conducted a retrospective population-based cohort study linking Colorado Birth Registry data and state immunization data of all live births between 2008 and 2016. The cohort was limited to singleton, first births. Multivariable logistic regression was used to assess associations between maternal and neonatal factors and influenza vaccination., Results: Among 126,763 births meeting criteria for inclusion, 50.2% were vaccinated against influenza by two years of age. Mothers of unvaccinated children were older (27 vs 26 years, p < 0.0001), married (67.8% vs 66.8%, p < 0.0001), with a college education (38.8% vs 37.2%, p < 0.0001). Influenza vaccination rates declined over time by birth year (30.5% in 2009 vs 6.8% in 2013, p < 0.0001). Children admitted to the NICU receiving oxygen with 72 h of birth were 20% less likely to be vaccinated (RR = 0.8, 95% CI: 0.67-0.96) after adjusting for maternal age, race/ethnicity, education and preterm birth. Conversely, premature births were associated with an increase in influenza vaccination by age two years (RR = 1.1, 95%CI: 1.05, 1.15)., Conclusions: Among a large population-based cohort of mother-infant pairs in Colorado using birth and immunization registry data, there were statistically significant differences in maternal factors between unvaccinated and vaccinated children with influenza in the first 2 years of life, but the differences were too small to be clinically significant. Children admitted to the NICU were 20% less likely to be vaccinated, highlighting the need to target influenza vaccination in this population once eligible. Ongoing studies are needed to explore factors associated with early influenza vaccination., (Copyright © 2019 Elsevier Ltd. All rights reserved.)