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We update an evidence-based clinical practice guideline for the administration of the dissociative agent ketamine for emergency department procedural sedation and analgesia. Substantial new research warrants revision of the widely disseminated 2004 guideline, particularly with respect to contraindications, age recommendations, potential neurotoxicity, and the role of coadministered anticholinergics and benzodiazepines. We critically discuss indications, contraindications, personnel requirements, monitoring, dosing, coadministered medications, recovery issues, and future research questions for ketamine dissociative sedation.