Abstract: Objective: To compare the short and long-term health outcomes, within a captured payer environment, of children exposed to one or more vaccines to those unexposed. Design: Birth cohort study. Setting: Integrated healthcare system in Michigan. Participants: 18,468 children born between 2000 and 2016 enrolled in the health system insurance plan. Main Outcome Measures: Development of a chronic health condition over time. Results: A total of 18,468 consecutive subjects met eligibility criteria for the study, of which 1,957 had no exposure to vaccination and 16,511 had received at least one vaccine during their enrollment in the plan with various levels of exposure. After multivariate adjustment, Cox proportional hazards modeling demonstrated that exposure to vaccination was independently associated with an increased risk of developing a chronic health condition (HR 2.53, CI 2.16-2.96). Of the chronic health conditions, exposure to vaccination was independently associated with an increased risk of asthma (HR 4.25, CI 3.23-5.59), autoimmune disease (HR 4.79, CI 1.36-16.94), atopic disease (HR 3.03, CI 2.01-4.57), eczema (HR 1.31, CI 1.13-1.52), and neurodevelopmental disorder (HR 5.53, CI 2.91-10.51). There were no chronic health conditions associated with an increased risk in the unexposed group. The overall probability of being free of a chronic health condition at 10-years of follow up was 43% in the group exposed to vaccination and 83% in the unexposed group. Conclusion: This study found that exposure to vaccination was independently associated with an overall 2.5-fold increase in the likelihood of developing a chronic health condition, when compared to children unexposed to vaccination. This association was primarily driven by asthma, atopic disease, eczema, autoimmune disease and neurodevelopmental disorders. This suggests that in certain children, exposure to vaccination may increase the likelihood of developing a chronic health condition, particularly for one of these conditions.