Most often depicted as the precursor to the much simpler and safer practice of Jennerian cowpox vaccination, the eighteenth‐century practice of inoculating against smallpox with the live virus reveals much about the way in which pre‐modern mothers and medics understood and made decisions about disease management in children. Examined from the perspective of those mothers who ultimately sanctioned its use and helped to advance the practice on English soil, despite a complex set of possible eventualities ‐ from uncertain conferral of immunity to death ‐ this article argues that provided an ‘English’ version of it was carried out in strict accordance with the age‐old doctrines of humoral medicine, mothers deemed it an entirely rational act devoid of ‘risk’ in our modern sense. These findings run counter to established narratives asserting blanket professionalization and medicalization of childcare during this period, and they nuance the role Lady Mary Wortley Montagu played in introducing the practice she had encountered in Turkey.