Background: Reducing risks and harms among people who inject drugs by, for example, Needle and Syringe exchange Programs (NSP) may be impeded in practice by, for example, policy restrictions, particularly in settings like Sweden where a zero-tolerance drug strategy prevails. In practice, risks and harms are produced through an interplay of multiple mutually reinforcing factors. Moreover, risk management strategies may constitute risks per se and generate new risks, potentially intensifying overall harm. This study aimed to increase our understanding of how such risks are generated in the lives of people who inject drugs. Methods: In 2022–2023, we interviewed 32 purposively selected research participants, primarily recruited through the Stockholm NSP. Drawing on actor-network theory, we analyzed the interviews to identify factors—constituent human and non-human actors—that constitute and generate risk and harm. These dynamics were conceptualized as risk-amplifying loops, in which harms are contingently enacted, may multiply, and the effects of policy and practice may become unintentional and unpredictable. Results: Four risk-amplifying loops were inductively elucidated: the Service deficit, Perpetrator-victim, Deprivation, and Solitude loops. In each, two actors—the drug and the person who injects drugs—were constituted differently. Furthermore, the loops were interlinked and more fully understood in relation to one another, forming a network that reflected the broader environment of injection drug use (IDU) in Sweden. Each loop was shaped and co-constituted by the prohibitionist framing of Swedish drug policy influencing access to services, the drug market, and the position of people who use drugs. Conclusions: Understanding drug-related harms as risk-amplifying loops highlights the emergent effects of the multiple and unfolding risks in the lives of people who inject drugs. This perspective facilitates discussion of impediments to effective harm reduction practices and points to potential sites for countermeasures and policy reform.