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The authors evaluated all available evidence on the use of propofol as an adjuvant for the treatment of resistant alcohol withdrawal syndrome (AWS) in comparison to other therapies. A comprehensive PubMed search (1966-December 2015) was conducted using the search terms propofol, alcohol withdrawal, and drug therapy. Articles were cross-referenced for other citations. Clinical studies, case series, and case reports published in the English language assessing the use of propofol in adult patients for treatment of AWS were reviewed for inclusion. Propofol is a sedative-hypnotic that exerts its actions through agonism of GABAA receptors at a different binding site than benzodiazepines and reduces glutamatergic activity through N-methyl-d-aspartase (NMDA) receptor blockade. Dosages from 5 to 100 μg/kg/minute reduced AWS symptoms with frequent development of hypotension and requirement for mechanical ventilation. Patients on propofol often experienced longer durations of mechanical ventilation and length of stay, which may be attributed to more-resistant cases of AWS. When propofol was compared with dexmedetomidine as adjuncts in AWS, both agents showed similar benzodiazepine- and haloperidol-sparing effects. Dexmedetomidine was associated with more numerical rates of bradycardia, while propofol was associated with more numerical instances of hypotension. Dexmedetomidine was used more frequently in nonintubated patients. The available data assessing the utility of propofol for AWS exhibited significant heterogeneity. Propofol may be useful in a specific population of patients with AWS, limited to those who are not clinically responding to first-line therapy with benzodiazepines. Specifically, propofol should be considered in patients who are refractory to or not candidates for other adjuvant therapies, patients already requiring mechanical ventilation, or those with seizure activity or refractory delirium tremens. In severe, refractory AWS, adjuvant therapy with propofol may be considered but requires further research to recommend its use either preferentially or as monotherapy., (© 2016 Pharmacotherapy Publications, Inc.)