There is growing acknowledgment that social, structural, and environmental forces produce vulnerability to health harms among people who inject drugs (PWID), and safer environment interventions (SEI) have been identified as critical to mitigating the impacts of these contextual forces on drug-related harm. To date, however, SEIs have been under-theorized in the literature, and how they minimize drug-related risks across intervention types and settings has not been adequately examined. This article presents findings from a systematic review and meta-synthesis of qualitative studies reporting PWID’s experiences with three types of SEIs (syringe exchange programmes, supervised injection facilities and peer-based harm reduction interventions) published between 1997 and 2012. This meta-synthesis seeks to develop a comprehensive understanding of SEIs informed by the experiences of PWID. Twenty-nine papers representing twenty-one unique studies that included an aggregate of more than 800 PWID were included in this meta-synthesis. This meta- synthesis found that SEIs fostered social and physical environments that mitigated drug-related harms and increased access to social and material resources. Specifically, SEIs: (1) provided refuge from street-based drug scenes; (2) enabled safer injecting by reshaping the social and environmental contexts of injection drug use; (3) mediated access to resources and health care services; and, (4) were constrained by drug prohibition and law enforcement activities. These findings indicate that it is critical to situate SEIs in relation to the lived experiences of PWID, and in particular provide broader environmental support to PWID. Given that existing drug laws limit the effectiveness of interventions, drug policy reforms are needed to enable public health, and specifically SEIs, to occupy a more prominent role in the response to injection drug use.