Background: State-mandated school entry immunization requirements in the United States play an important role in achieving high vaccine coverage and preventing outbreaks of vaccine-preventable diseases. Most states allow non-medical exemptions that let children remain unvaccinated on the basis of personal beliefs. However, the ease of obtaining such exemptions varies, resulting in a patchwork of state vaccination exemption laws, contributing to heterogeneity in vaccine coverage across the country. In this study, we evaluate epidemiological effects and spatial variations in non-medical exemption rates in the context of vaccine 1 policies. Methods and Findings:We first analyzed the correlation between non-medical exemption rates and vaccine coverage for three significant childhood vaccinations and found that higher rates of non-medical exemptions were associated with lower vaccination rates of school-aged children in all cases. We then identified a subset of states where exemption policy has recently changed and found that the effects on statewide non-medical exemption rates varied widely.Focusing further on Vermont and California, we illustrated how the decrease in non-medical exemptions due to policy change was concurrent to an increase in medical exemptions (in CA) or religious exemptions (in VT). Finally, a spatial clustering analysis was performed for Connecticut, Illinois, and California, identifying clusters of high non-medical exemption rates in these states before and after a policy change occurred. The clustering analyses show that policy changes affect spatial distribution of non-medical exemptions within a state.Conclusions: Our work suggests that vaccination policies have significant impacts on patterns of herd immunity. Our findings can be used to develop evidence-based vaccine legislation.Immunization requirements for school-entry date back to 1922 and have played a key role in 1 achieving high levels of vaccine coverage against communicable diseases in the United States 2 [1]. This patchwork of childhood immune protection, however, is punctured by a hetero-3 geneous set of state-specific vaccination exemption rules. Medical exemptions to mandated 4 vaccinations are available in all 50 states, and 47 offer non-medical exemptions in some form. 5Namely, 18 states offer personal belief exemptions for those who object to vaccinations for 6 philosophical or moral reasons. In the remaining states offering non-medical exemptions, 7 they are limited to religious beliefs. In the remaining three states (California, Mississippi, 8 and West Virginia), only medical exemptions are available. While this has been the policy 9 in Mississippi and West Virginia for decades [2], the ban on non-medical exemptions in Cal-10 ifornia (enacted by CA Senate Bill 277 in January 2016) was motivated by the 2015 measles 11 outbreak in the state [3] in which suboptimal vaccination rates in school-aged children was 12 an important factor in the magnitude of the outbreak [4]. 13The ease of obtaining non-medical exemptions vari...