OBJECTIVES: To describe the frequency and determinants of self-medication for symptoms of sexually transmitted infections (STI) in a female sex worker (FSW) population. To present a methodology exploring the best predictors as well as the interactions between determinants of self-medication. METHODS: A cross-sectional survey of 4153 FSW carried out in Peru. The prevalence of self-medication was estimated from the subsample of participants who had experienced symptoms of STI in the past 12 months (n=1601), and used successive logistic regression models to explore the determinants. RESULTS: Self-medication prevalence for a reported symptomatic episode during the past 12 months was 32.1% (95% CI 29.8 to 34.6). It was negatively correlated with work in brothels (adjusted odds ratio (OR) 0.51, 95% CI 0.28 to 0.93; p=0.028) and awareness of STI services available for FSW (adjusted OR 0.49, 95% CI 0.29 to 0.81; p=0.006). Other determinants were organised at different levels of proximity to the outcome creating pathways leading to self-medication. CONCLUSIONS: The importance of the staggered analysis presented in this study resides in its potential to improve the understanding of associations between determinants and, consequently, the targeting of interventions. The awareness of STI services available for FSW increases access to health care, which in turn decreases self-medication. In addition, the sharing of information that takes place between brothel-based FSW was also related to a diminishing prevalence of self-medication. These two main predictors provide an opportunity for prevention programmes, in particular those designed to be led by peers.