This guidance document was developed by Mexico City’s Clínicas Especializadas Condesa based on their experience implementing the ImPrEP trial in Mexico (2018–2021) to enable providers to integrate pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) for HIV prevention into services using a client-centred approach. The guidance is grounded in evidence and describes the use of antiretrovirals as PrEP and PEP, differentiated pre-screening counseling for different populations, clinical and behavioural screening for PrEP, PrEP counselling and follow-up, harm reduction, adolescent use of PrEP and when and how to stop taking PrEP.