To our knowledge, this is the first reported comparison of clonidine with benzodiazepine in the management of acute alcohol withdrawal syndrome. In a double-blind trial, 61 men experiencing acute alcohol withdrawal were randomly assigned to receive clonidine or chlordiazepoxide over a 60-hour treatment period. Clonidine was more effective than chlordiazepoxide at reducing alcohol withdrawal scale scores, systolic blood pressures, and heart rates over the entire study period. Clonidine was as good as chlordiazepoxide at improving Cognitive Capacity Screening Exam, Hamilton Anxiety Rating Scale, and Self-Rating Scale scores. Adverse drug reactions reported by each group were similar, though less nausea and vomiting were observed in the clonidine group. Clonidine may represent a new alternative agent for the management of acute alcohol withdrawal syndrome.