STUDY OBJECTIVE Gabapentin has been proved to be beneficial in promoting abstinence, decreasing alcohol cravings, and improving mood and sleep quality when given at higher doses; however, data are limited regarding the efficacy and safety of using high-dose gabapentin as part of the treatment of alcohol withdrawal syndrome (AWS). The aim of this study was to evaluate the impact of highdose gabapentin on benzodiazepine requirements, alcohol withdrawal symptoms, and hospital length of stay in patients hospitalized with AWS. DESIGN Retrospective cohort study. SETTING Large academic medical center. PATIENTS All adults presenting to the emergency department between January 2015 and April 2018 with a diagnosis of severe AWS (Clinical Institute Withdrawal Assessment for Alcohol Scale, Revised [CIWA-Ar] score ≥ 15) and prescribed the institution's alcohol withdrawal agitated delirium protocol were eligible for inclusion in the study. Of these, 50 patients who received high-dose gabapentin (≥ 1800 mg/day) in the first 48 hours of hospital admission (treatment group) were propensity score-matched to 50 patients who did not receive gabapentin (control group). MEASUREMENTS AND MAIN RESULTS Patients who received high-dose gabapentin required a significantly lower overall amount of benzodiazepines (mean AE SD 109.5 AE 53.4 mg vs 88.5 AE 35.6 mg [lorazepam equivalents], p=0.023) and had a significantly lower mean CIWA-Ar score (10.1 AE 4.7 vs 7.7 AE 3.9, p=0.010) and maximum CIWA-Ar score (16.0 AE 7.0 vs 12.6 AE 6.1, p=0.016) on day 3 of hospitalization. The high-dose gabapentin regimen was well tolerated, without an increased risk of oversedation, compared with the control group (Richmond Agitation-Sedation Scale score < À1: 34% in the treatment group vs 20% in the control group, p=0.115). Patients receiving high-dose gabapentin had a shorter length of hospital stay (7.4 AE 4.0 days vs 6.0 AE 2.6 days, p=0.034) and