Project Summary Xylazine is an emerging serious threat to people who inject drugs (PWID). Xylazine and fentanyl drug mixtures elevate risk overdose and because xylazine is not an opioid, naloxone does not reverse its effects. Despite the increasing presence of xylazine in overdose deaths across the US, there is limited epidemiologic research focused on characterizing the prevalence and risk factors of its use in settings where mortality data indicates a known elevated risk. Although there has been a marked uptick of severe wounds and necrosis among those using drugs that contain xylazine, the specific drug use practices or other characteristics related to the development of wounds are not known. The goal of this research is to generate urgently needed evidence to understand the prevalence, risk factors, knowledge, and harm reduction practices associated with xylazine use and the development of wounds among PWID, in order to effectively inform practice and raise awareness among the affected communities, health care and harm reduction service providers and the public regarding the health risks associated with xylazine. We propose a mixed methods approach using respondent-driven sampling to identify and survey approximately n=300 PWID in Baltimore and n=40 qualitative interviews with those who use xylazine, health care and harm reduction providers. We will estimate the prevalence and correlates of both intentional and suspected xylazine use and examine xylazine-specific overdose knowledge, beliefs and practices. We will determine the prevalence of wounds associated with xylazine use and the association between HIV infection, drug use practices and wounds. We will also characterize barriers to accessing wound care using qualitative methods. This research on a sudden emerging illicit drug will generate time-sensitive knowledge that will directly contribute to preventing the harmful consequences associated with xylazine emergence. We will translate our findings and conduct broad dissemination, working with local stakeholders, partner organizations, and governmental agencies to inform overdose and treatment programs.