The mean risk of acquiring HIV after an occupational exposure, injecting drug use or sexual exposure varies from < 0.1 to 3%. A high plasma HIV-RNA of the source increases the risk of each of the exposures. Other factors, such as the volume of the inoculum involved to which the individual was exposed, other sexually transmitted diseases and ruptures of mucous membranes are associated with a higher risk of HIV transmission. Based on the calculated risk, post-exposure prophylaxis (PEP) should be recommended. In the Netherlands, prescription of PEP in the occupational setting is a standard procedure and has proved to be feasible. This was associated with a high percentage (62%) of mild and reversible toxicity and a small percentage (2%) of serious adverse events related to antiretroviral drugs, i.e. nephrolithiasis (due to indinavir) and toxic hepatitis (due to nevirapine). In The Netherlands so far no HIV-seroconversions have been recorded after an occupational accident.