Prophylactic Fictions traces a prehistory for what I term inoculation insecurity, by which I mean a constellation of political and cultural anxieties surrounding the legitimacy, safety, and efficacy of a developing medical procedure used to preserve the health of its subject in advance of infection. I read a collection of pamphlets, poetry, plays, essays, and novels that witness the evolution of this procedure from early eighteenth-century variolation (inoculation by smallpox matter) to late eighteenth-century vaccination (inoculation by cowpox matter). The culture wars inaugurated by Edward Jenner’s revolution of preventative medicine through vaccination grappled with the right of the government and the medical establishment to literally puncture the bodies of citizens on the grounds that England was “threatened,” be it by French radicalism or by foreign bodies and objects crossing English borders. Bringing this rich archive to bear on readings of canonical novels like Daniel Defoe’s Journal of the Plague Year and Bram Stoker’s Dracula resituates them at the locus of intense debates about the persistently insecure relationship between the body (individual and social) and the state. Attention to the transitions in the co-constituent domains of medicine and literature during the eighteenth and nineteenth centuries reveals that inoculation’s preventative function has never been purely a biological issue. At stake were not only the changes in medical technology and practice but also the professionalization and institutionalization of medicine itself. My project recalibrates the axes by which we tend to narrate the history of medicine: vaccine skepticism was not simply a refusal of medical innovation but a direct challenge to the state’s cooptation and misuse of medicine in the name of “national security.” Can and should the state be able to monitor, regulate, or even make compulsory health interventions based purely on the need to prevent imagined threats? Literary and cultural production in this period captures the conflicting ways in which health threats were imagined and secured.