In 2010, the centre for the AIDS Programme of Research in South Africa (CAPRISA)004 and iPrEx trials (microbicide gel containing tenofovir and oral pill containing tenofovir-emtricitabine, respectively) demonstrated that antiretroviral preexposure prophylaxis (PrEP) reduced the risk of HIV acquisition among high-risk individuals. To determine the facilitators and barriers to PrEP provision by health-care providers, we conducted an online, quantitative survey of Massachusetts-area physicians following the publication of the CAPRISA and iPrEx results. We assessed awareness and comprehension of efficacy data, prescribing experience, and anticipated provision of oral and topical PrEP among physicians, as well as demographic and behavioral factors associated with PrEP awareness and prescribing intentions. The majority of HIV specialists and generalist physicians were aware of data from these PrEP trials and able to correctly interpret the results, however, correct interpretation of findings tended to vary according to specialty (i.e., HIV specialists had greater awareness than generalists). In addition, provider concerns regarding PrEP efficacy and safety, as well its ability to divert funds from other HIV prevention resources, were associated with decreased intentions to prescribe both oral and topical PrEP. Findings suggest that a substantial proportion of physicians who may have contact with at-risk individuals may benefit from interventions that provide accurate data on the risks and benefits of PrEP in order to facilitate effective PrEP discussions with their patients. Future studies to develop and test interventions aimed at health-care providers should be prioritized to optimize implementation of PrEP in clinical settings.