School-based compulsory vaccination laws have provoked debates over the legitimacy of government coercion versus the scope of parental rights. A key point of contention in these school vaccination laws are provisions known as exemption clauses that allow some parents to enroll their children in school unimmunized for reasons other than medical conditions. For more than three decades Mississippi and West Virginia stood apart as the only two US states that did not offer nonmedical exemptions to school vaccination laws. But other states seem to be moving in this direction, such as California, which in 2015 eliminated nonmedical exemptions following the Disneyland measles outbreak. The apparent shift creates an opportune moment to look at the experiences of Mississippi and West Virginia. Through a review of legislative histories, legal rulings, media accounts, and interviews with health officials in the two states, we consider the reasons for and consequences of their allowing only medical exemptions and the prospects their approach holds out for other states that may wish to emulate it. The experiences of these two states suggest that contrary to conventional wisdom, it may be politically tenable to limit exemptions to only medical reasons without damaging either the stature of public health or the immunization system.