We assessed the potential for anticipated changes in sexual risk-taking behaviour following hypothetical administration of a low-efficacy preventive HIV vaccine. We developed a survey and collected self-reported data from 158 HIV-negative volunteers in a cohort undergoing prescreening for Phase I/II HIV vaccine trials in Soweto. Overall, 22% reported they might use condoms less frequently; 9% reported that they might increase their frequency of sex with casual/anonymous partners; and 55% reported their sexual partners might want to use condoms less frequently knowing they were vaccinated. Multivariate analyses revealed that anticipated decrease in condom use was predicted by poor comprehension and by young age. Individuals may increase their risk-taking behaviour knowing that a vaccine would provide only incomplete protection against HIV transmission. In HIV vaccine trials and future vaccination programmes, education and risk-reduction counselling will be needed for vaccinated individuals and their partners, and mass media education campaigns may be necessary.