The genre of the plague treatise, still little studied, testifies to the cultural transformations that swept western Eurasia after the Black Death apocalypse of the mid-fourteenth century, with recurrent outbreaks for centuries thereafter. Ottoman contri-butions to this genre are exemplary: they allow us to track the emergence of an imperi-al-scientific early modernity. This article presents the most comprehensive and innova-tive Islamicate plague treatise extant, Taşköprīzāde Aḥmed’s (d. 1561) Treatise on Healing Epidemic Diseases. Therein the celebrated Ottoman polymath makes a strong case, advanced by arguments both religious and rational, for occult science as the most em-pirical method for preventing and curing the plague. To this end, he devotes the theo-retical first half of the treatise to a critique of fatalist scholars and sufis, who prefer tawakkul to tasabbub, or blind faith to “scientific method”; the practical second half is devoted to what he considers to be the most medically effective scien-tific discipline of his era, lettrism (ʿilm al-ḥurūf)—a Neopythagorean science encapsu-lating the new “cosmological imaginary” of Western early modernity generally, wherein the world was seen by many thinkers and doers as a mathematical and hence magically tractable text. Our distaste for occult science notwithstanding, Taşköprīzāde must here be named another early modern empiricist.