BackgroundSex workers have high incidences of HIV and other sexually transmitted diseases. Although, interventions targeting sex workers have shown to be effective, evidence on which strategies are most cost-effective is limited. This study aims to systematically review evidence on the cost-effectiveness of sexual health interventions for sex workers on a global level. It also evaluates the quality of available evidence and summarizes the drivers of cost effectiveness.MethodsA search of published articles until May 2018 was conducted. A search strategy consisted of key words, MeSH terms and other free text terms related to economic evaluation, sex workers and sexual and reproductive health (SRH) was developed to conduct literature search on Medline, Web of Science, Econlit and the NHS Economic Evaluation Database. The quality of reporting the evidence was evaluated using the CHEERS checklist and drivers of cost-effectiveness were reported.ResultsOverall, 19 studies met the inclusion criteria. The majority of the studies were based in middle-income countries and only three in low-income settings. Most of the studies were conducted in Asia and only a handful in Sub-Saharan Africa and Latin America. The reviewed studies mainly evaluated the integrated interventions, i.e. interventions consisted a combination of biomedical, structural or behavioural components. All interventions, except for one, were highly cost-effective. The reporting quality of the evidence was relatively good. The strongest drivers of cost-effectiveness, reported in the studies, were HIV prevalence, number of partners per sex worker and commodity costs. Furthermore, interventions integrated into existing health programs were shown to be most cost-effective.ConclusionThis review found that there is limited economic evidence on HIV and SRH interventions targeting sex workers. The available evidence indicates that the majority of the HIV and SRH interventions targeting sex workers are highly cost-effective, however, more effort should be devoted to improving the quality of conducting and reporting cost-effectiveness evidence for these interventions to make them usable in policy making. This review identified potential factors that affect the cost-effectiveness and can provide useful information for policy makers when designing and implementing such interventions.Electronic supplementary materialThe online version of this article (10.1186/s12962-018-0165-0) contains supplementary material, which is available to authorized users.