Attention to how women are differentially impacted within harm reduction environments is salient amidst North America's overdose crisis. Harm reduction interventions are typically 'gender-neutral', thus failing to address the systemic and everyday racialized and gendered discrimination, stigma, and violence extending into service settings and limiting some women's access. Such dynamics highlight the significance of North America's first low-threshold supervised consumption site exclusively for women (transgender and non-binary inclusive), SisterSpace, in Vancouver, Canada. This study explores women's lived experiences of this unique harm reduction intervention.Ethnographic research was conducted from May 2017 to June 2018 to explore women's experiences with SisterSpace in Vancouver's Downtown Eastside, an epicenter of Canada's overdose crisis. Data include more than 100 hours of ethnographic fieldwork, including unstructured conversations with structurally vulnerable women who use illegal drugs, and in-depth interviews with 45 women recruited from this site. Data were analyzed in NVivo by drawing on deductive and inductive approaches.The setting (non-institutional), operational policies (no men; inclusive), and environment (diversity of structurally vulnerable women who use illegal drugs), constituted a space affording participants a temporary reprieve from some forms of stigma and discrimination, gendered and social violence and drug-related harms, including overdose. SisterSpace fostered a sense of safety and subjective autonomy (though structurally constrained) among those often defined as 'deviant' and 'victims', enabling knowledge-sharing of experiences through a gendered lens.SisterSpace demonstrates the value and effectiveness of initiatives that engage with socio-structural factors beyond the often narrow focus of overdose prevention and that account for the complex social relations that constitute such initiatives. In the context of structural inequities, criminalization, and an overdose crisis, SisterSpace represents an innovative approach to harm reduction that accounts for situations of gender inequality not being met by mixed-gender services, with relevance to other settings.