Studies suggest that dexmedetomidine-an intravenous central-acting ?2-adrenergic agonist that effectively reduces anxiety among critically ill patients-is being used in patients with severe alcohol withdrawal. However, evidence supporting its use is limited, and it is not approved for this indication. To assess the effect of dexmedetomidine on severe alcohol withdrawal symptoms and to compare its use with benzodiazepines alone. A retrospective, cohort study of 77 patients admitted to the adult medical intensive care unit with severe alcohol withdrawal between January 1, 2009, and October 31, 2013. The difference in lorazepam equivalents and Clinical Institute Withdrawal Assessment for Alcohol scores in the 24 hours before and after initiation of dexmedetomidine therapy. The frequency of dexmedetomidine use increased dramatically between 2009 and 2013 (16.7% vs 82.4%; p = 0.01). Initiation of dexmedetomidine therapy was associated with significant improvements in Clinical Institute Withdrawal Assessment for Alcohol scores over corresponding 24-hour intervals (14.5 vs 8.5; p < 0.01). Benzodiazepine use also decreased, but the difference was not statistically significant at 24 hours (p = 0.10). Dexmedetomidine was well tolerated, requiring discontinuation of therapy in only 4 patients (10.5%). Dexmedetomidine use was also associated with significantly longer hospitalizations (p < 0.01). Dexmedetomidine initiation was associated with a reduction in short-term alcohol withdrawal symptoms in patients in the intensive care unit, with only a few patients experiencing adverse events. However, its use was also associated with longer hospitalizations. Further research is necessary to evaluate whether dexmedetomidine is efficacious or cost-effective in severe alcohol withdrawal.