The objective of this study was to elucidate factors that predicted the initiation of HIV postexposure prophylaxis (PEP) for blood or body fluid exposures evaluated at Rhode Island emergency departments (EDs). The study involved a retrospective review of patient visits to all civilian Rhode Island EDs for these exposures from 1995 to mid-2001. Multivariate logistic regression models were created to evaluate predictors of the offering and the acceptance and receipt of HIV PEP from 1996 to 2001. The search identified 3622 patients who sustained a blood or body fluid exposure. Of these, 43.8% were health care workers (HCWs) and 57.2% were not HCWs. Most (52.0%) of the exposures were nonsexual. HIV PEP was offered to 21.0% and accepted and received by 9.4% of all patients. HIV PEP was offered more often after significant exposures, exposures to known HIV-infected sources, when time elapsed after the exposure was shorter, if the patients were HCWs, adults, presented to a teaching hospital, presented during the latter years of the study, or sustained nonsexual exposures. Once offered HIV PEP, patients who were male, adult, sustained a significant exposure, knew the source was HIV infected, sustained a nonsexual exposure, or were HCWs had a greater odds of accepting and receiving HIV PEP. Even when controlling for exposure significance, HIV status, and time elapsed since the exposure, several factors such as gender and type of hospital that are unrelated to the exposure appeared to influence the initiation of HIV PEP. ED providers should ensure that these factors do not inappropriately restrict its initiation.