Abuse potential, psychomotor and cognitive side effects, and pharmacologic synergism with alcohol limit the use of benzodiazepines in outpatient settings. Although positive results have been reported in the few prior studies of Depakote for alcohol withdrawal, methodological flaws limit the generalizability of the findings. This study compared Depakote to benzodiazepines in the treatment of alcohol withdrawal. Sixteen patients in moderate alcohol withdrawal were randomized to receive a standard benzodiazepine detoxification, Depakote detoxification, or Depakote detox plus maintenance. Screening and assessment instruments were used to quantify baseline and follow-up data. Results show that Depakote may be a safe and effective alternative to benzodiazepines in select patient populations. It also may be an effective alternative for outpatient detoxification, as it has no abuse potential, pharmacologic synergy with alcohol, or substantial cognitive or psychomotor side effects. The study also suggests that Depakote may have use as a post-detox relapse prevention agent because the 6-week Depakote maintenance group had greater abstinence rates and more improvement in overall drinking outcomes than either detox-only group. Patients with histories of seizures, delirium tremens, unstable medical or psychiatric conditions, or polysubstance dependence are best served in a medically managed inpatient setting with standard benzodiazpine detoxification protocols. Future studies should examine whether Depakote is effective in more severe withdrawal, its safety in patients with significant liver disease, and its acceptable use for outpatient detoxification. 1 figure, 1 table, 21 references