Safe Injection Self-Efficacy is associated with HCV and HIV seropositivity among people who inject drugs in the San Diego-Tijuana border region.

We found profound inequalities between Tijuana and San Diego SISE, likely attributable to differential risk environments. Associations with fentanyl and polysubstance co-injection, injection frequency, and both HIV and HCV seropositivity suggest that SISE contribute to blood-borne infection transmission risks in Tijuana. SISE reflects an actionable intervention target to reduce injection risk behaviors, but structural interventions are required to intervene upon the risk environment.