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To date there are no published studies on the effectiveness of HIV post-exposure prophylaxis (PEP) after sexual exposure. However, as emergency physicians we are faced with the dilemma of assessing the risk of HIV transmission and providing appropriate care for patients who present to us after sexual assault. Current practice in UK emergency departments and genitourinary clinics varies from trust to trust. There is no direct evidence that HIV PEP after rape prevents transmission or is cost effective. However, there may be certain rape cases where HIV PEP should be prescribed or at least considered. While we wait for more definitive clinical studies, HIV PEP after rape should be considered on a case to case basis. This article aims to provide emergency physicians with current scientific evidence on HIV PEP enabling them to make an informed decision on when HIV PEP is indicated after rape.