INTRODUCTION: Transgender people in South Africa are disproportionately affected by HIV, discrimination and stigma. Access to healthcare and health outcomes are poor. Although integrating gender-affirming healthcare with differentiated HIV prevention, care and treatment services has shown improvement in HIV service uptake and health outcomes among transgender people, evidence is lacking on the implementation of differentiated service delivery models in southern Africa. This article describes a differentiated service delivery model across four South African sites and transgender individuals who access these services. We assess whether hormone therapy (HT) is associated with continued use of pre-exposure prophylaxis (PrEP) and viral load suppression. METHODS: In 2019, differentiated healthcare centres for transgender individuals opened in four South African districts, providing gender-affirming healthcare and HIV services at a primary healthcare level. Routine programme data were collected between October 2019 and June 2021. Descriptive statistics summarized patient characteristics and engagement with HIV prevention and treatment services. We conducted a multivariate logistic regression analysis to determine whether HT was associated with viral load suppression and PrEP continued use. RESULTS: In the review period, we reached 5636 transgender individuals through peer outreach services; 86% (4829/5636) of them accepted an HIV test and 62% (3535/5636) were linked to clinical services. Among these, 89% (3130/3535) were transgender women, 5% (192/3535) were transgender men and 6% (213/3535) were gender non-conforming individuals. Of those who received an HIV test, 14% (687/4829) tested positive and 91% of those initiated antiretroviral treatment. Viral load suppression was 75% in this cohort. PrEP was accepted by 28% (1165/4142) of those who tested negative. Five percent (161/3535) reported ever receiving HT through the public healthcare system. Service users who received HT were three-fold more likely to achieve viral load suppression. We did not find any association between HT and continued use of PrEP. CONCLUSIONS: A differentiated HIV and gender-affirming service delivery model at a primary healthcare level is feasible and can enhance service access in South Africa. HT can improve HIV clinical outcomes for transgender people. As trust is established between the providers and population, uptake of HIV testing and related services may increase further.