This article provides for the first time a robust quantitative estimate of the amount of syphilis infection in the population of London in the later eighteenth century. A measure of the cumulative incidence of having ever been treated for the pox by the age of 35 is constructed, providing an indicator of over 20 per cent syphilitic infection. The principal primary sources are hospital admissions registers, augmented with an analysis of London’s workhouse infirmaries. A range of potentially confounding factors are taken into account, including the contemporary conflation between syphilis and other sexually transmitted infections, patients who shunned hospitals in favour of private treatment, possible double-counting of patients, institutional patients who may have hailed from outside London, and the complexity of establishing what should constitute the ‘at-risk’ population of London for this period. Cultural and medical historians have demonstrated considerable pre-occupation with venereal disease in the texts of the eighteenth century, while demographic and epidemiological historians, lacking any quantitative evidence, have tended to ignore the disease. This article can now demonstrate for the first time just how extensive syphilis was likely to have been and, by doing so, offer an original contribution to major debates in the history of sexuality and the demography of early modern London.