The Center for the AIDS Programme of Research in South Africa (CAPRISA) 004 and Pre-exposure Prophylaxis Initiative (iPrEx) studies demonstrated that topical or oral chemoprophylaxis could decrease HIV transmission. Yet to have an appreciable public health impact, physicians will need to be educated about these new HIV prevention modalities. Massachusetts physicians were recruited via e-mail to complete an online survey of their knowledge and use of HIV prevention interventions. Data were collected before (July-December, 2010) (n=178) and after (December, 2010-April, 2011) (n=115) the release of iPrEx data. Over the two time intervals, knowledge of oral PrEP significantly increased (79% to 92%, p<0.01), whereas knowledge about topical microbicides was already high (89% pre-iPrEx). Post-iPrEx, specialists were more knowledgeable about oral PrEP (p<0.01) and topical microbicides (p<0.001) than generalists. The majority of the respondents would prefer to prescribe topical microbicides (75%) than oral PrEP (25%; p<0.001), primarily because they perceived fewer side effects (95%). Respondents indicated that PrEP should be available if it were a highly effective, daily pill; however, ongoing concerns included: potential drug resistance (93%), decreased funds for other forms of HIV prevention (88%), medication side effects (83%), and limited data regarding PrEP's clinical efficacy (75%). Participants indicated that formal CDC guidelines would have the greatest impact on their willingness to prescribe PrEP (96%). Among Massachusetts physicians sampled, chemoprophylaxis knowledge was high, but current experience was limited. Although topical gel was preferred, responses suggest a willingness to adapt practices pending additional efficacy data and further guidance from normative bodies. Educational programs aimed at incorporating antiretroviral chemoprophylaxis into physicians' HIV prevention practices are warranted.