OBJECTIVE: The primary aim of the study was to evaluate the effectiveness and tolerability of aripiprazole on motor and vocal tics in children and adolescents with Tourette's disorder (TD). The secondary aim was to assess the response of TD-associated behaviors to aripiprazole exposure. METHODS: This was an 8-week, open-label trial with flexible dosing strategy of aripiprazole in children and adolescents with TD. A total of 72 patients, aged 6-18 years, participated in the 8-week trial. The Yale Global Tic Severity Scale (YGTSS), the Clinical Global Impressions-Tics (CGI-Tics), and the Child Behavior Checklist (CBCL) were compared at the baseline, weeks 2 and 4, and end point. The side effects of aripiprazole, electrocardiogram (ECG), and body mass index (BMI) were evaluated. RESULTS: Over the 8-week trial, aripiprazole administration was associated with a significant decrease in total tic severity as measured by the YGTSS (50.3% reduction by week 8). The mean scores of motor tic in the YGTSS were 17.42 +/- 4.83, 12.93 +/- 3.76, 8.39 +/- 3.70, and 6.75 +/- 3.95 at baseline, weeks 2 and 4, and end point. A significant decrease in the scores was observed in week 2 compared to the baseline, and the scores continued to decrease for the remainder of the study period (degrees of freedom [df ] = 3, F = 96.02, p = 0.000). The mean phonic tic scores were 12.71 +/- 4.60, 8.53 +/- 3.26, 6.10 +/- 2.50, and 3.63 +/- 2.20 at baseline, weeks 2 and 4, and end point, respectively. A significant change was observed during week 2 compared to the baseline, and this change continued for the rest of the study period (df = 3, F = 95.16, p = 0.000). Significant improvement was also observed according to the CGI-Tics severity. The mean CGI-Tics severity score was 4.77 +/- 1.69 at baseline and decreased to 2.20 +/- 1.39 at end point (t = 10.70, p = 0.000). A significant reduction of behavior symptoms was noticed according to the CBCL and its subscales between baseline and end point. The majority of subjects tolerated aripiprazole well. The extrapyramidal symptoms (EPS) during this study were negligible. In all 21 (29.2%) of the 72 participants complained of nausea and 19 (26.4%) of them reported sedation. There was no significant difference of BMI between the two phases (df = 64, t = -0.94, p = 0.352). There were no significant changes in laboratory results. ECG monitoring revealed no significant impact on cardiac conduction by aripiprazol. CONCLUSION: In this preliminary open-label trial, aripiprazole showed effectiveness in treating tic symptoms without causing significant weight gain or other serious side effects. Aripiprazole could be an option for TD cases that do not respond to conventional therapies. Further controlled, double-blind studies are warranted.