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Heroin overdose, more accurately termed ‘heroin-related overdose’ due to the frequent involvement of other drugs, is the leading cause of mortality among regular heroin users. (Degenhardt et al., 2010) Heroin injectors are at greater risk of hospital admission for heroin-related overdose (HOD) in the eastern United States where Colombian-sourced powder heroin is sold than in the western US where black ‘tar’ heroin predominates. (Unick et al., 2014) This paper examines under-researched influences on HOD, both fatal and non-fatal, using data from a qualitative study of injecting drug users of black tar heroin in San Francisco and powder heroin in Philadelphia Data were collected through in-depth, semi-structured interviews carried out in 2012 that were conducted against a background of longer-term participant-observation, ethnographic studies of drug users and dealers in Philadelphia (2007–12) and of users in San Francisco (1994–2007, 2012). Our findings suggest three types of previously unconsidered influences on overdose risk that arise both from structural socio-economic factors and from the physical properties of the heroin source-types: 1) retail market structure including information flow between users; 2) marketing techniques such as branding, free samples and pricing and 3) differences in the physical characteristics of the two major heroin source forms and how they affect injecting techniques and vascular health. Although chosen for their contrasting source-forms, we found that the two cities have contrasting dominant models of drug retailing: San Francisco respondents tended to buy through private dealers and Philadelphia respondents frequented an open-air street market where heroin is branded and free samples are distributed, although each city included both types of drug sales. These market structures and marketing techniques shape the availability of information regarding heroin potency and its dissemination among users who tend to seek out the strongest heroin available on a given day. The physical characteristics of these two source-types, the way they are prepared for injecting and their effects on vein health also differ markedly. The purpose of this paper is to examine some of the unexplored factors that may lead to heroin-related overdose in the United States and to generate hypotheses for further study. [ABSTRACT FROM AUTHOR]