This essay explores the history of smallpox variolation and vaccination with particular emphasis on the contributions of Thomas Jefferson to the spread of both methods in the United States. The research draws mainly upon contemporary histories of the disease and modern medical insights, as well as primary sources in the form correspondence between Thomas Jefferson and his contemporaries. Jefferson's motivation in performing his own experiments with variolation and vaccination becomes clear when considering his Eastern and British forerunners, and the enthusiasm with which he writes on the subject points to his emotional involvement. This research makes clear the significance of Jefferson's experiments to scientific progress and the importance of his efforts to alert the American people of the procedures' value.