Despite scientific research supporting the use of vaccination to protect against disease, some individuals choose not to vaccinate their children for religious or political reasons. Vaccination is a topic of heated debate today, but this debate actually started in early-eighteenth-century America when a Puritan minister promoted the practice during an outbreak of smallpox in Boston. By the end of the 1721 epidemic, inoculation (a primitive form of vaccination) saved almost 300 people, but it also ignited fierce protests. Many Puritans viewed inoculation as distrust in God, the spread of disease frightened colonists, and the meddling of ministers in the affairs of “learned men” outraged physicians. This inoculation debate provides a case study for analyzing the influence of religious beliefs on public views of inoculation before the development of modern medicine. The study examines a set of digitized documents from the debate using an online tool to perform a “distant reading,” quantifying the language used by both supporters and opponents of inoculation. The resulting graphs demonstrate the relative frequencies of the use of religious and secular language in the debate and reveal patterns in the language of ministers and physicians. In addition, the study compares this quantitative analysis to a traditional close reading of the texts to suggest limitations of a quantitative analysis and refine conclusions on the relationship between religion and science during the debate. Future research can employ the text analysis methods developed in this historical study to further research the extent of cultural influence on the vaccination debate.