Using a population based self-controlled case series study design we examined data on 834,740 children in the province of Ontario, Canada. We observed that when comparing to SGA10 term children (term children born in the lowest 10th percentile of weight for a given gestational age), relative incidence of emergency room visits and admission in the 3 d post 2 mo vaccination progressively decreased in near term (relative incidence ratio 0.89 (95% CI 0.74-1.07)) and very premature children [(0.67(0.49-0.93)]. When compared with all term children this decrease in risk is not statistically significant. We speculate that the immune response is reduced in premature children resulting in reduced adverse events. This is masked when comparing to all term children because the reduced birth weight of premature children results in a comparatively increased dose of vaccine. This in turn results in an increased immune response and risk of immediate adverse reactions. Future studies of immune response in premature children should examine the impact of weight at the time of immunization.