Abstract Current guidelines on HIV prevention for MSM emphasise the need for ‘combination prevention’ based on context-specific understandings of HIV risk. MSM in South Africa are a population with a high risk of HIV infection, however there is little research available on the drivers of this risk. In the context of a focus on combination prevention, this paper argues that effective HIV prevention for MSM in South Africa requires an understanding of the factors at multiple ‘distances’ from individuals that contribute to HIV risk. Based on qualitative research with MSM in Cape Town, South Africa, we situate HIV risk using a socio-ecological framework and identify factors at distal, proximal, and personal, levels that contribute to MSM’s high risk of HIV infection. By understanding the interactions and linkages between risk environments and the risk situations in which HIV is transmitted, HIV prevention programmes will be more effectively able to address the multiple drivers of HIV risk in this population.