Vaccine Hesitancy is a critical public health issue that threatens global health security, increases rates of transmission of deadly diseases, and poses additional infectious risk to everyone. This dissertation uses records from the National Archives and Records Administration of the United States, National Archives of Mexico, World Health Organization, multiple Presidential Libraries, and an assortment of digital records to examine the historical roots of vaccine hesitancy. I argue that the choice to delay vaccination or outright refusal of vaccination often constitutes a form of political protest. This anti-vaccine sentiment has historically functioned as political protest that opposes American and Western presence in developing countries. Illustrative case studies of Pakistan and Mexico between 1947 and 1990 illustrate how the manner in which vaccines are distributed within the context of Cold War disease eradication campaigns can influence vaccine hesitancy. Horizontal vaccine programming in Mexico wherein vaccines were distributed using a robust, native public health infrastructure found more epidemiological success than Pakistani vaccination programs that relied on vertically-oriented, Western-led mass vaccination programming to mitigate the burden of infectious diseases including smallpox and polio. Rhetorical analysis of archival vaccine-related media in these countries also reflects the politicized nature of Cold War vaccine hesitancy. Additionally, this dissertation broadly considers the array of weaponry in the American diplomatic arsenal and compares the diplomatic utility of vertical mass vaccination campaigns with military assistance that was also provided to developing nations in the pursuit of American anti-communist goals in the midst of the Cold War. I argue that certain programmatic ambiguities in Cold War American Foreign Policy led to the production of a uniquely militarized form of American diplomacy. An examination of biosurveillance networks constructed to support the global eradication of smallpox and subsequently replicated to eradicate polio illustrate the long-standing historical intersection between public health programming and military force that underlie historical and modern vaccine hesitancy.