BACKGROUND Levetiracetam (Keppra) is a commonly prescribed anticonvulsant that has been shown to attenuate alcohol consumption in an open-label study of treatment-seeking, alcohol-dependent subjects. METHODS Here we performed a 42-day placebo-controlled, double-blind, randomized crossover trial to evaluate the effects of levetiracetam on moderate to heavy drinkers receiving either a low (500-1000 g/d) or a moderate (1000-2000 g/d) dose. Electronic diaries were used to monitor daily ethanol intake. RESULTS Across the entire group, there was no effect of levetiracetam on drinking irrespective of dose, treatment order, family history, ethnicity, sex, or adverse effects. However, a median split of the data based on the number of drinks consumed while taking placebo revealed that levetiracetam significantly increased drinking in the lower drinking subjects (n = 23, P = 0.05, t = 2.07) while having no effect on drinking in the higher half (n = 23, P = 0.75, t = 0.32). Preliminary stratification based on common polymorphisms associated with alcoholism and impulsivity indicated that subjects with alcoholism-associated alleles may drink even more while taking levetiracetam. CONCLUSIONS Our data suggest that levetiracetam is not an appropriate treatment for non-treatment seeking alcohol abusers and can, in fact, increase their consumption of alcohol.