Alcohol abuse and alcohol withdrawal syndrome are major problems in the United States. This retrospective chart review assessed efficacy and safety of propofol plus dexmedetomidine used in combination as adjunctive therapy to benzodiazepines compared with either agent used alone in the treatment of severe alcohol withdrawal. Patients admitted to the intensive care unit and experiencing severe alcohol withdrawal between September 1, 2015 and September 30, 2018 were assessed for eligibility. Primary end points were change in the revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA‐Ar) score and incidence of bradycardia and hypotension. The combination of propofol and dexmedetomidine was associated with a change in CIWA‐Ar score of −10.4 (95%CI −13.5 to −7.3) points compared with −4.7 (95%CI −6.6 to −2.8) points with propofol and −4.4 (95%CI −7.4 to −1.4) with dexmedetomidine (P = .21). Bradycardia was experienced by 11.1% of patients receiving the combination, 15.4% of patients receiving propofol, and 28.6% of patients receiving dexmedetomidine (P = .40). Patients receiving dexmedetomidine experienced hypotension at a rate of 21.4% compared with 22.2% of patients receiving the combination and 38.5% of patients receiving propofol (P = .08). Patients in the combination group also had a shorter length of hospital and intensive care unit stay and shorter time to extubation when compared with the propofol and dexmedetomidine groups. Although no statistical significance was found, the combination was associated with better efficacy and safety outcomes than produced by either agent used alone.