A variety of situations, either accidental or linked to high-risk behaviour, raise concerns about potential infection from contact with the blood or genital secretions of a person who may be HIV-infected. Antiretroviral post-exposure prophylaxis is offered to prevent establishment of HIV infection. As of 2011, what is the evidence for the efficacy of antiretroviral post-exposure prophylaxis? Under what circumstances is this treatment justified? To answer these questions, we reviewed the available evidence, based on the standard Prescrire methodology. The evidence for the efficacy of rapidly initiated prophylaxis following exposure comes mainly from one case-control study on health professionals injured while treating HIV-positive patients. Treatment with zidovudine for 3 to 4 weeks was associated with a risk of HIV seroconversion that was 5 times lower than among those not treated. The main clinical practice guidelines recommend the use of antiretroviral treatments that are already well established for chronic HIV infection as post-exposure prophylaxis. A typical regimen combines HIV-protease inhibitors (ideally lopinavir + ritonavir) with a fixed-dose combination of two nucleoside (or nucleotide) reverse transcriptase inhibitors (emtricitabine + tenofovir or lamivudine + zidovudine). Certain antiretrovirals are best avoided as first-choice therapy due to their adverse effects: abacavir due to the risk of serious allergic reactions; atazanavir due to the risk of jaundice and torsades de pointes. Non-nucleoside reverse transcriptase inhibitors (such as efavirenz) frequently cause adverse cutaneous and neurosensory adverse effects, especially during the first weeks of treatment. The main adverse effects of antiretrovirals are gastrointestinal. Diarrhoea is common with lopinavir. Antiretrovirals interact with many other drugs. HIV-protease inhibitors reduce the efficacy of hormonal contraceptives. The Iopinavir + ritonavir + zidovudine + lamivudine combination has been used for a long time to treat pregnant women. No evidence of teratogenicity has been shown.The antiretrovirals atazanavir, emtricitabine, nelfinavir, nevirapine and tenofovir can also be used but there is less experience with their use during pregnancy. Post-exposure treatment should be started as soon as possible: wash and rinse the wound; initiate antiretroviral therapy within 48 to 72 hours, without waiting to obtain all the information required for risk assessment; reassess the infection risk 2 to 4 days later. Risk assessment should be based on the type and circumstances of exposure, and the source person's serological HIV status and viral load if the individual is known to be HIV-infected and receiving treatment.This information should be obtained urgently or estimated on the basis of HIV infection is still possible despite post-exposure prophylaxis.Therefore, in order to avoid transmitting the virus to others, anyone exposed and potentially infected should be advised against unprotected sex or blood donation for 3 months, until serological evidence has been obtained that they have not been infected. In practice, the many situations in which the risk of infection is uncertain should be managed on a case-by-case basis, with the patient's involvement, weighing the probability of HIV transmission against the adverse effects of a one-month course of antiretroviral therapy.