Background:: There are significant gender differences in injection drug practices and relative risks involved for women who inject drug compared with men. This qualitative study aims to explore the social, contextual, and behavioral dimensions of injecting practices among women who inject drugs.

Methods:: Participants were selected by purposive venue-based sampling from a syringe exchange program in 2012–2013. In-depth interviews were conducted with 26 women to elicit detailed perspectives regarding injection drug use practices and women-focused decision-making. All interviews were transcribed verbatim and analyzed with Atlas.ti.

Results:: Participant’s mean age was 43.2 years, 48% Caucasian, 36% African American, and 16% Latina, poorly educated, mostly single, and heroin self-injectors. Three themes emerged; a) transitioning from non-injection to injection drug use; b) patterns and variations of initiation to injecting; and c) shifting toward autonomy or reliance on others. Women were predominantly influenced to transition to injection drug use by other women with their claims that injecting was a way to curtail their daily drug expenditure. More than half the women received their first injection from another woman in their social network rather than a male sexual partner. Self-injecting women exhibited agency around the circumstances of injection safety and potential risks. Other women revealed that their inability to inject themselves could and did make them dependent on others for unsafe injection practices.

Conclusions:: The finding that many women were influenced to transition to injection drug use and receive the first injection from a woman is contrary to literature claims that male sexual partners introduce and initiate women to injection drug use. Self-injecting women possessed capacity to act in a way that produced the results they wanted, not sharing prepared drugs or injecting equipment. In stark contrast, women assisted with injections could and did make them vulnerable to unsafe injecting. Findings support early prevention strategies that discourage women’s transition from non-injection to injection and development of female peer-driven experiential interventions to dispel myths for non-injection women and to increase personal capability to self-inject for women who require assistance with injecting, to reduce injection-related harm.