Since 1998, French HIV guidelines have recommended use of HIV prophylaxis after unprotected sex (postexposure prophylaxis, or PEP) with an HIV-positive partner. To characterize factors associated with lack of PEP knowledge in an HIV-positive population, a cross-sectional survey was conducted of 737 French HIV-positive outpatients followed in AIDS care units of 2 regions accounting for 60% of French AIDS cases. Information was collected through face-to-face interviews. The sample was weighted to improve national validity. Median age was 41 years, 73.2% of patients were male, and 8.5% reported HIV-related risk behaviors. Those who knew about PEP and those who did not were compared with chi2 tests and logistic regression. One third of the sample had never heard of PEP. In multivariate analysis, lack of PEP knowledge was associated with older age, low educational level, unstable housing, unawareness of current HIV laboratory data, and lack of ability to confide in nurse and to seek out information from various sources. The increased number of people living with HIV infection as a chronic disease raises new challenges for its secondary prevention. Preventive programs aimed at HIV-positive individuals and their sexual partners are strongly needed.