Background: Robust population size estimates (PSEs) for female sex workers (FSW) and other key populations in South Africa face multiple methodological limitations, including inconsistencies in surveillance and programmatic indicators; this has consequently challenged appropriate allocation of resources and benchmark-setting necessary to an effective HIV response. A 2013-14 Integrated Biological and Behavioral Surveillance (IBBS) survey from South Africa showed alarmingly high HIV prevalence among FSW in South Africa's three largest cities of Johannesburg (71.8%), Cape Town (39.7%), and eThekwini (53.5%). The survey also included several multiplier-based population size estimation (PSE) methods.