INTRODUCTION: Updated guidelines from the WHO recommend antiretroviral treatment for adults with HIV at any CD4 count and daily oral pre-exposure prophylaxis (PrEP) for people at substantial risk of HIV infection. However, implementation challenges may hinder the ability of programmes to translate these recommendations into successful practice. This demonstration project is the first to integrate PrEP and immediate treatment (ITx) for female sex workers (FSWs) in South Africa to answer operational research questions. METHODS AND ANALYSIS: This is a prospective cohort study where the main outcome is retention at 12 months. The study population is recruited into two arms across two urban sites: (1) PrEP for HIV-negative FSWs (n=400) and (2) ITx for HIV-positive FSWs with CD4 greater than national guidelines (n=300). We investigate process and other health indicators, uptake and use of PrEP and ITx through qualitative research, and evaluate cost-effectiveness analysis combined with estimates of impact through epidemiological modelling. ETHICS AND DISSEMINATION: The Treatment And Prevention for female Sex workers in South Africa (TAPS) Project was designed as an implementation study before emtricitabine/tenofovir disoproxil fumarate was licenced as an indication for PrEP in South Africa. Therefore, clinical trial requirements for ethical and South African Medicines Control Council approvals were followed. Results will be disseminated to participants, local health officials and other stakeholders, as well as in peer-reviewed journals and at conferences.