Whereas many infectious diseases are spread through casual contact and contagion, HIV transmission results from risk behaviors that involve close and often intimate contact. As a result, the transmission of HIV is structured by the social relationships within which these contacts are embedded. Hence, social network analysis is especially suitable for understanding the AIDS epidemic. This paper reports the results of a field experiment that compares a network-based HIV prevention intervention, termed a “Peer-Driven Intervention” (PDI), with the standard form of street-based outreach intervention. The results suggest that the network intervention outperforms the standard approach with respect to number of people accessed, reductions in self-reported levels of HIV risk behavior and cost. Finally, the analysis focuses on the network structure of drug injectors and discusses the implications of these structures for understanding both the spread of HIV through social networks and the design of HIV-prevention interventions. The results show that certain network features, including geographically extensive networks and an abundance of ties across ethnic boundaries, genders, ages and drug preferences, can further the spread of HIV. Ironically, these are also the network features that increase the effectiveness of network-based HIV-prevention interventions. Thus, we show that network interventions work best precisely when they are most needed, that is, when network structures facilitate the spread of HIV