For neonates identified as at increased risk of acquiring HIV perinatally, the optimal postnatal prophylaxis regimen is not known. Current United States Public Health Service guidelines recognize that combination postnatal prophylaxis may be considered in some situations but that there are little data regarding the effectiveness and safety of any postnatal regimen besides zidovudine. The actual use of combination postnatal regimens in the United States has not previously been described. We conducted a national, Web-based survey between December 2009 and January 2010 to describe the percent of providers who prescribe combination postnatal prophylaxis, the antiretroviral combinations they used, and the risk factors that might elicit combination postnatal prophylaxis. 472 known or possible perinatal HIV providers were queried; 42% (n = 197) responded and 68% of respondents (134) were eligible to complete the survey. Sixty-two percent (n = 83) of participating providers reported use or recommendation of combination postnatal prophylaxis in the last year. Three drugs, zidovudine, lamivudine and nevirapine, comprised 77% of first-choice combination regimens. Lopinivir-ritonivir (LPV/RTV) was included in 16% of all reported regimens. Combination postnatal prophylaxis was strongly preferred in patient-based scenarios with additional risk factors for perinatal HIV transmission.