Health officials attest that immunizations are among the most successful interventions in public health. However, there remains a substantial unvaccinated population in the United States. We analyzed how state-level vaccination exemption laws affect immunization rates and the incidence of preventable disease. We measured the association between each component of state kindergarten vaccination exemption laws and state vaccination exemption rates from 2002 to 2012, using the Centers for Disease Control and Prevention’s annual school assessment reports. We found that policies such as requiring health department approval of nonmedical exemptions, requiring a physician to sign an exemption application, and having criminal or civil punishments for noncompliance with immunization requirements had a significant effect in reducing vaccine exemptions. Our exemption law effectiveness index identified eighteen states with the most effective laws and nine states with the least effective ones. The most effective states had lower incidences of pertussis, compared to other states. For policy makers interested in decreasing the number of vaccine exemptions in their state, our findings are of particular interest.