This book explores the response to a new scientific advance in medicine three hundred years ago to understand how this discourse revealed religious, racial, anti-intellectual, and other ideologies the first time documented vaccinations were introduced in America. This text serves as a case study that examines the historic discourses surrounding the implementation of a new prevention technique, smallpox inoculation, to prevent the devastating epidemics of smallpox that had visited the new colonies since their start on the American continent. Using this detailed analysis of the arguments surrounding the project in early America, the author examines the various arguments that circulated in the 1720s regarding the project. When compared to today's pandemic, this study argues that Americans over-react and complicate scientific applications not with logical scientific perspectives or even with ethical views, but instead bring exaggerated claims founded on uniquely American historical, religious, racial, territorial, and political ideologies. America's First Vaccination will be of interest to anyone interested in American history, the history of medicine, cultural studies, and a comparison to current pandemic events.