This article includes updated British Association for Sexual Health and HIV guidelines for HIV post-exposure prophylaxis (PEP). This guideline group does not recommend PEP for any type of exposure if the index individual/partner is a PWH on ART for at least 6 months with an undetectable viral load and good adherence. By contrast, PEP should be routinely offered for: receptive anal intercourse involving an index partner of unknown status or known to be HIV positive with an unknown/detectable viral load; receptive vaginal sex with a partner known to be HIV positive with an unknown/detectable viral load; IDU equipment sharing if the injection partner is a PWH with unknown/detectable viral load; and following a sharps or mucosal splash involving an index case known to be HIV positive with an unknown/detectable viral load. PEP should be considered for insertive vaginal sex with an index partner who is a PWH with unknown/detectable viral load; and for insertive anal intercourse with an index partner of unknown status. PEP is generally not recommended in all other scenarios, including sharps and splash injuries, bites, injection equipment sharing, and vaginal intercourse when the index case is untested and from a high-risk group (unless specific extenuating case/local factors increasing risk are present). The first-line recommended regimen is tenofovir disoproxil/emtricitabine plus raltegravir for 28 days (PEP use may be extended if high-risk sexual exposures occur during the last 2 days of the course). Routine renal and liver function testing is unnecessary unless clinically indicated or if baseline results are abnormal. Final HIV testing is recommended at a minimum of 45 days after PEP completion. For people on PrEP, PEP decision-making is guided by PrEP adherence, length of time since last PrEP dose, and site(s) of exposure.