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Aims: To compare two inpatient symptom-triggered pharmacological treatments of acute alcohol withdrawal (AWS) (clomethiazole vs. clonazepam). Methods: Prospective observational comparison within a quality improvement project. Because of a need for extra precautions against complications such as seizures and severe respiratory complaints, patients with a history of withdrawal seizures or complications with clomethiazole in their history were automatically assigned to the clonazepam group. The remaining patients were alternately assigned either to the clonazepam group ( n = 38 altogether) or the clomethiazole group ( n = 36). Rescue medication could consist of adding either extra clonazepam or clomethiazole. Effectiveness was measured by Clinical Global Impression Scale, Revised Clinical Institute Withdrawal Assessment for Alcohol Scale, Mainz Alcohol Withdrawal Scale, Essen Self-Assessment-Alcohol Withdrawal and attrition rate. Safety and tolerability was estimated from adverse clinical events. Secondary outcome values were heart rate, blood and pulse pressure. Results: There were no significant differences between the treatments with respect to primary and secondary effectiveness measures, safety or tolerability or duration of medication treatment. Both reduced the severity of initial withdrawal symptoms below 20% up to the ending of withdrawal medications. No withdrawal seizure or delirium occurred. Conclusion: Both score-driven treatments were equally effective, safe and well tolerated in this setting. This is the first study demonstrating the utility of clonazepam in the treatment of AWS syndrome.