During the colonial period sexually transmitted infections (STIs) came to be recognised as a major public health problem in African cities. Thus, STI control and urban modernisation became deeply entangled as authorities redrew spatial and social boundaries to manage populations and their cross-cultural interaction. Public health measures, urban planning and policing were part of a coordinated effort to neutralise the potential impact of rapidly growing African urban migration on the Belgian Congo’s ‘model’ capital Leopoldville. While STI control was facilitated by new drugs (arsenicals, sulfonamides and antibiotics) to treat syphilis, chancroid, gonorrhoea and chlamydia (bacterial STIs), the effects of the 1929 economic crisis and urban social change illustrated the limits of colonial authority. Redesigning urban spaces and repressive measures to curb polygyny and prostitution operated in a parallel fashion with the expansion of health coverage, new treatments and awareness campaigns. To gain a better understanding of the evolution of STI incidence among African urban populations during the colonial period between 1910 and 1960, extensive archival records and secondary literature were consulted to assess the interplay between improved screening, diagnostic and therapeutic methods with demographic and social change. They show that STI rates, probably peaked during the pre-1929 period and apart from a short period in the early 1930s associated with mass screening, declined until becoming residual in the 1950s. Reflecting upon sanitary interventions and their broader dimensions, the article analyses the evolution of treatment regimes and their impact in the changing urban organisation and environment of the colony’s capital. ; publishersversion ; published