We calculated the Poisson-regression-adjusted relative risk (RR) of new influenza infection by vaccination, prior infection, and vaccination after prior infection in a large Japanese birth cohort, using data from ≤89,253 children aged 6 months to 3 years. The effectiveness of risk reduction (1 – RR) by vaccination at ages 1.5-3 years was 21%-31%. The RR of new infection after prior infection vs. no prior infection was 2.58-19.3 at age 1-3 years. An analysis of the 1 – RR data stratified by having at least one senior sibling and/or attending nursery school revealed that vaccination reduced the RR by 22%-40%. The 1 – RR of new infection was 21% in 3-year-old children who were vaccinated after prior infection. All these findings are statistically significant. The results consistently indicate that, regardless of having at least one senior sibling, attending nursery school, and/or being previously infected with influenza, infants and toddlers will benefit from influenza vaccination.