In the late sixteenth century, a number of university-educated surgeons in Spain began producing vernacular surgical manuals designed to provide the most recent knowledge in surgical treatments to practicing surgeons who could not read Latin. These texts are notable in their number and diversity of authors as well as for the fact that many include discussions of diagnosis and treatment of diseases including peste (plague) and morbo gallico (syphilis). These two diseases are, in a way, hallmarks of the premodern era; plague arose in epidemic form in the fourteenth century and morbo gallico in the late fifteenth century. As “new” diseases that often appeared changeable in nature, both gave rise to continued debates over their causes, the means by which they spread, and best methods of treatment. As diseases that produced external and visible symptoms of rashes, sores or buboes, they increasingly fell under the care of surgeons. This paper analyzes the way these diseases were understood and treated by surgeons in late sixteenth-century Spain. While many studies have examined the initial responses of medical personnel to these diseases in their earliest centuries, there has been less attention paid to later evolving ideas of causation, spread and treatment. These vernacular texts are significant in providing a window onto how experience and empiricism shifted perceptions of each disease, and how learned practitioners sought to codify and pass on this knowledge to their present and future colleagues.