Background: Initiation of a relapse prevention medication is crucial at the end of alcohol detoxification. This study aimed to examine the efficacy and safety of topiramate for alcoholism in patients receiving a residential treatment program of alcohol detoxification and post-acute treatment. Methods: This was a 12-week, randomized, double-blind, placebo-controlled trial of topiramate for alcoholism in patients receiving a residential treatment program. Individuals with DSM-IV alcohol dependence with minimal withdrawal were enrolled. Participants were randomly assigned to receive either 100-300. mg/day of topiramate or placebo. Primary outcomes were given as percentages of heavy drinking days and time to first day of heavy drinking. Other drinking outcomes, craving, and health-related quality of life were evaluated. Results: A total of 106 participants were randomized to receive topiramate (n=53) or placebo (n=53). Twenty-eight participants of the topiramate group (52.8%) and 25 participants of the placebo group (47.2%) completed the study. Averaged over the trial period, there was no significant difference between groups on the mean percentages of heavy drinking days [1.96 (-1.62 to 5.54), p=.28]. Log rank survival analysis found no difference of time to first day of heavy drinking between topiramate and placebo groups (61.8 vs. 57.5 days, respectively; χ2=0.61, d.f.=1, p=.81). Other secondary outcomes were not significantly different between groups. Conclusions: By using a conservative model for data analysis, we could not detect the effectiveness of topiramate in this particular population. As the sensitivity analysis showed a trend of its benefit, further studies in larger sample sizes are still warranted. © 2013 Elsevier Ireland Ltd.