A disproportionate number of new HIV infections in South Africa are among female sex workers; pre-exposure prophylaxis (PrEP) for HIV prevention is freely available to female sex workers in the country, but unique barriers challenge PrEP persistence. TB HIV Care, a large South African non-profit organisation that provides daily oral PrEP (tenofovir disoproxil fumarate and emtricitabine), has implemented multiple strategies to improve PrEP persistence. We aimed to evaluate the effect of different implementation strategies on PrEP persistence in a large-scale real-world setting.