Venereal disease was commonplace among free and enslaved populations in colonial Caribbean societies. This article considers how contemporaries (both in the empire and metropole) viewed venereal infection and how they associated it with gendered notions of empire and masculinity. It further explores how creole medical practices evolved as planters, slaves, and tropical physicians treated sexually transmitted infections. Yet what began as a familiar and customary affliction was seen, by the late eighteenth century, as a problematic disease in the colonies. As medical theory evolved, placing greater attention on behaviour, British abolitionists focused on the sexual excesses and moral failings of Caribbean slaveholders, evidenced by their venereal complaints. The medicalization of venereal infection and its transition from urbane affliction to stigmatized disease helps explain a key problem in imperial history: how and why West Indian planters became demonized as debauched invalids whose sexual excesses rendered them fundamentally un-British. The changing cultural meanings given to venereal disease played an important role in giving moral weight to abolitionist attacks upon the West Indian slave system in the late eighteenth century. This article, therefore, indicates how changing models of scientific explanation had significant cultural implications for abolitionists, slaveholders, and enslaved people alike.