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Background: Xylazine is in 99% of the fentanyl supply in Philadelphia, PA and is on the rise throughout the United States. Perspectives about this emerging crisis among people who use opioids (PWUO) and harm reduction workers are lacking. Methods: We conducted focus groups with PWUO and harm reduction workers in Philadelphia, PA. Discussions focused on xylazine's impact on PWUO. Transcripts were coded for thematic analysis. Results: Themes across focus groups included xylazine withdrawal, wounds, safety concerns, and overdose response implications. Participants emphasized extreme xylazine withdrawal and the difficulty of withdrawal management. Groups explored potential roles of first responders in addressing xylazine-related wounds. PWUO were receptive to receiving help, but many harm reduction workers expressed reservations about partnering with police. Discussion: Results underscore the impact of xylazine withdrawal on PWUO. Emerging information on withdrawal management should be shared among care providers to identify optimal protocols. Safety-planning with PWUO should be explored, but structural interventions are imperative. While there may be a role for first responders in delivering harm reduction interventions, it is important to recognize historical harms by first responders against PWUO. [ABSTRACT FROM AUTHOR]