Female Sex Workers (FSWs) in sub-Saharan Africa (SSA) have been identified as a high-risk group for the spread of HIV/AIDS, with those in poor areas and “HIV hotspots” being especially vulnerable. Research has shown that the primary reason poor women engage in commercial sex work is financial instability. Given these challenges, poor women require support over and above HIV prevention education. We propose to test the impact of adding economic empowerment (EE) components to traditional HIV risk reduction (HIVRR) to reduce new incidence of sexually transmitted infections (STIs) and of HIV among FSWs in Rakai and Masaka districts in Uganda. Guided by social-cognitive and asset theories, the study provides an avenue for FSWs to explore alternative means of safe and sustainable income to replace sex work. The study is informed by a previously tested microfinance (MF) intervention for FSWs in Mongolia, a pilot study conducted with FSWs in Masaka and Rakai, surveillance studies by RHSP, and EE interventions among AIDS-affected families in Uganda. Using a cluster-design we will randomly assign 990 FSWs from 33 matched town centers to one of three study arms (11 town centers in each condition): (1) A control arm comprising of treatment as usual (TAU) for FSWs in the study area bolstered with 4 evidence-based sessions of HIVRR provided by local providers (n=330); or (2) A treatment arm including TAU, 4 sessions of HIVRR, combined with receipt of a matched savings account (HIVRR+S) to be used on short- and/or long-term consumption and skills development as per participants’ own discretion (n=330); or (3) A treatment arm including TAU, 4 sessions of HIVRR, combined with a matched savings account to be used on short-term and/or long term consumption and skills development as per a participant’s own discretion plus 6 sessions of financial literacy and 8 mentoring sessions for supportive transition to alternative income options (HIVRR+S+FLM) (n=330). This RCT study’s aims are to: Aim1: Examine the impact of a financial savings-led MF intervention using HIVRR+S and HIVRR+S+FLM on HIV biological and behavioral outcomes in FSWs (Primary outcomes: women’s cumulative incidence of biologically- confirmed STIs and reported number and proportion of unprotected sexual acts with regular and paying partners; Secondary outcomes: women’s rate of new HIV cases, proportion of monthly income from sex and non- sex work, reported number and proportion on preventive behaviors, and for HIV+ women only, viral load as a marker of ART adherence). Aim 2: Examine intervention mediation and effect modification to assess whether primary outcomes are mediated/moderated by participant characteristics; whether key theory-driven variables and Behavioral Economics measures mediate/moderate intervention outcomes. Aim 3: Qualitatively and quantitatively examine implementation in each study condition; and Aim 4: Assess the cost and cost-effectiveness of the HIVRR+S and HIVRR+S+FLM intervention ...