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Alcohol withdrawal syndrome, if untreated, can lead to potentially life-threatening complications. Benzodiazepines are the drugs of choice for the treatment of alcohol withdrawal syndrome. We aimed to compare the symptoms-triggered approach and fixed-dose approach of benzodiazepine administration for treatment of alcohol withdrawal syndrome in regard to the health care utilization measured by the total dose of benzodiazepines, length of hospital stays, and 90-day readmissions rate. A single-center prospective non-randomized controlled trial included all patients diagnosed with alcohol withdrawal syndrome. The group of patients admitted between October 1, 2019, and September 30, 2020, were treated with the fixed-scheduled approach (n = 150), while all patients admitted between November 1, 2020, to October 31, 2021, were treated with the symptoms-trigger approach (n = 50). The fixed-dose approach group showed a significant higher 90-day readmissions rate (HR: 2.61; 95% CI = 1.18, 6.84; p = 0.01). Kaplan–Meier survival analysis showed a significantly shorter duration to the first readmission in the fixed-scheduled approach group (HR: 2.3; 95% CI = 5.6, 1.16; p = 0.02). The symptoms-triggered approach group required a significantly lower dose of diazepam (40 mg vs. 10 mg; p < 0.01) and a higher dose of thiamine (800 mg vs. 600 mg; p < 0.01). Length of hospital stay was significantly increased in the symptoms-triggered approach group (3.9 vs. 2.2 days; p < 0.01). The use of a symptoms-triggered approach to treat alcohol withdrawal syndrome was associated with a lower 90-day readmission rate, prolonged period to the first readmission, and reduced total dose of benzodiazepines, but longer length of hospital stays. The symptoms-triggered approach is safe, cost-effective, and associated with reduced alcohol dependence relapse. •The use of the symptoms-triggered approach for treatment of alcohol withdrawal syndrome was associated with reduction of 90-day readmissions, increased duration to the first readmission, and reduced the total dose of benzodiazepines.•Compared to fixed doses of benzodiazepam, the symptoms-triggered approach for treatment of alcohol withdrawal syndrome may increase length of hospital stay.•The use of the symptoms-triggered approach for treatment of alcohol withdrawal syndrome is safe and was not associated with increased in-hospital adverse events.