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Although some individuals who present for antiretroviral postexposure prophylaxis (PEP) had a 1-time exposure to human immunodeficiency virus (HIV), others may be recurrently risky. Given that preexposure prophylaxis (PrEP) has been shown to be efficacious, identification of those individuals who present for PEP who might benefit from PrEP is important to decrease HIV acquisition in high-risk individuals. While inclusion criteria for PrEP have been developed, there is a paucity of data to help clinicians determine which PEP users are at highest risk for HIV acquisition and therefore should be offered PrEP. We will discuss the rationale for using PrEP after PEP use, and will focus on the assessment of PEP users who may benefit from PrEP.