Background Selective mass treatment of STIs may lead to a durable reduction in the prevalence of STIs or a temporary reduction associated with an increased probability of antimicrobial resistance emerging. Methods We searched PubMed and Google Scholar for studies evaluating the impact of mass STI treatment on the long-term prevalence of chlamydia, gonorrhoea, syphilis and chancroid. The primary outcomes were the long term (≥3 months post the intervention) impact of the intervention on prevalence/incidence of the STI and on antimicrobial resistance. Results Our search yielded 269 studies, of which 4 met the inclusion criteria. With the exception of the Carletonville study, where this was not assessed, three of the four studies found that intensive STI treatment was associated with a reduced prevalence of the targeted STI during or immediately after the intervention. In all four studies, there was no evidence that the intense treatment had a long-term effect on prevalence. In the only study where this was assessed, the intensive use of penicillin to reduce gonococcal prevalence was associated with the emergence of reduced susceptibility to penicillin in N. gonorrhoeae. Conclusion The available evidence suggests that mass treatment of chlamydia, gonorrhoea and syphilis in high prevalence populations is only associated with a temporary reduction in the prevalence of these infections and may select for antimicrobial resistance.