["Addiction, Volume 121, Issue 5, Page 1227-1236, May 2026. ", "\nAbstract\n\nBackground and aims\nXylazine, an alpha‐2 agonist used in veterinary anesthesia, is increasingly detected in the illicit opioid supply but little is known about the patient level factors associated with xylazine in non‐fatal opioid overdose. This study aimed to determine the demographic and clinical factors associated with xylazine detection among emergency department (ED) patients with opioid overdose.\n\n\nDesign\nObservational study. The Toxicology Investigators Consortium (ToxIC) Fentalog Study is a multicenter, prospective cohort of adult patients with suspected opioid overdose. This analysis included patients enrolled from September 2020 to September 2023.\n\n\nSetting\nIn this multicenter study, participating sites included 10 institutions across 9 states in 4 regions of the United States (US): Northeast, Southeast, Midwest and West.\n\n\nParticipants\nPatients were eligible for Fentalog Study inclusion if they were at least 18 years old, had a suspected opioid overdose and had waste blood available for toxicologic analysis. Only patients with qualitative serum detection of illicit opioids and/or xylazine were included in the final cohort. Of 5554 patients screened, 1289 were eligible for Fentalog Study inclusion.\n\n\nMeasurements\nBased on results of liquid chromatography with a quadrupole time‐of‐flight mass spectrometer (LCQTOF‐MS) and/or liquid chromatography with a triple quadrupole mass spectrometer (LC‐QQQ‐MS), patients were categorized into those with xylazine detected (positive cases) and without xylazine detected (negative controls). To determine clinical variables associated with xylazine detection, the primary outcome of interest was qualitative detection of xylazine on serum sampling by LCQTOF‐MS.\n\n\nFindings\nXylazine was detected in 238 patients. Patients with xylazine were primarily male (78%), white (48%), non‐Hispanic (82%) and located in the Northeast US (75%). Bradycardia on initial ED vital signs was associated with higher likelihood of xylazine detection (adjusted odds ratio = 2.11, 95% confidence interval = 1.06–4.06).\n\n\nConclusions\nXylazine detection among emergency department opioid overdose patients appears to be more prevalent in the Northeast US and bradycardia appears to be a statistically significant clinical predictor.\n\n"]