Histories of medicine and vaccinology routinely reference the Ottoman Empire with regard to Lady Mary Wortley Montagu, her children's variolation, and the transmission of this knowledge throughout Britain and thereafter Europe. Few, however, follow the empire's ongoing relationship with vaccination after the Montagu family's departure. This article examines this aspect of Ottoman medical history by noting how Jenner's advances diffused back into the empire and then presenting and analyzing how imperial, medical, and even community leaders began to both educationally condition the population and gradually enact legislation that mandated vaccination. Owing to severe infrastructural, personnel, and financial deficits, instability, and popular fears and trepidation, the empire's aspirations to achieve universal vaccination were far from realized by the time of its early 1920s demise-especially throughout largely rural Anatolia. Ottoman institutional, educational, and legislative advances, however, collectively prepared the ground for the succeeding Turkish republic and its public health agenda. Given the republic's promotion of its efforts to modernize Turkey amid its mutual initiatives of nationbuilding, the empire's histories of providing this foundation are also sometimes overlooked.