BACKGROUND Social marginalization and stigmatization in usual medical care setting may refrain female sex workers (FSWs) from seeking usual medical care for sexually transmitted infections in Hong Kong. GOAL To evaluate the cost-effectiveness of using an outreach approach for treatment and prevention of gonorrhea and chlamydia among FSWs. STUDY DESIGN A decision tree was designed to simulate the outcomes of 2 alternatives: (1) outreach service providing treatment of gonorrhea and chlamydia and counseling to FSWs (outreach arm) and (2) no outreach service (control arm). Five tiers of outcomes were estimated for each study arm: (1) total direct medical cost, (2) number of FSWs infected with gonorrhea, (3) number of new cases of gonorrhea in clients transmitted by FSWs, (4) number of FSWs infected with chlamydia, and (5) number of new cases of chlamydia in clients transmitted by FSWs. Clinical inputs were estimated from literature, and cost analysis was conducted from the perspective of a public health organization. RESULTS Compared to the control group, the marginal savings per new case of infection averted (marginal cost divided by marginal cases of infection) of the outreach group were $10,988 (US dollars) per case of gonorrhea averted in FSWs, $685 per case of gonorrhea averted in clients, $9643 per case of chlamydia averted in FSWs, and $220 per case of chlamydia averted in clients ($1=7.8 Hong Kong dollars). CONCLUSIONS An outreach clinic is potentially less costly and more effective in preventing transmission of gonorrhea and chlamydia between FSWs and their clients in Hong Kong.