To conduct a pilot study to examine topiramate for the treatment of weight gain associated with olanzapine in manic adolescents with bipolar disorder. We conducted a 12-week double-blind randomized placebo-controlled pilot study of topiramate (300-400 mg/day) versus placebo in manic youth (ages 10-18 years) with bipolar disorder who were treated with olanzapine (10-20 mg/day). The primary outcome measure was gender- and weight-normed change in body mass index (BMI z-score). Thirty manic adolescents were treated with olanzapine and were randomized to either topiramate (n = 16) or placebo (n = 14). There was a significantly greater increase in BMI z-scores in the placebo group (0.28 standard deviations [SDs]) compared with the topiramate group (0.10 SDs) when analyzed by longitudinal regression (p = 0.049). The placebo group had greater increases in raw BMI and weight (2.25 kg/m2 and 6.9 kg, respectively) compared with the topiramate (0.99 kg/m2 and 2.9 kg) group (p = 0.011 for BMI, p = 0.016 for weight). The most common adverse events in the topiramate group were headache (n = 7, 44%), gastrointestinal upset (n = 3, 19%), and muscle stiffness (n = 3, 19%). Topiramate may minimize the weight gain associated with olanzapine treatment in adolescents with bipolar disorder. Moreover, topiramate in combination with olanzapine was well tolerated. Larger studies that are adequately powered are necessary to determine the efficacy of topiramate for second-generation antipsychotic-related weight gain. ClinicalTrials.gov Identifier number NCT00394095.