Objective: Glutamate is considered a target for treating obsessive-compulsive disorder (OCD). The efficacy and safety of the nutritional supplement of N-Acetylcysteine (NAC) as an adjuvant to serotonin reuptake inhibitor (SSRI) for treating children and adolescents with OCD has never been examined. Method: This was a 10-week randomized double-blind placebo-controlled clinical trial with 34 OCD outpatients. The patients received citalopram plus NAC or placebo. Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Pediatric Quality of Life Inventory (PedsQL™) were used. Adverse effects were monitored. Results: YBOCS score was not different between the two groups at baseline, but the score was different between the two groups at the end of this trial (P<0.02). The YBOCS score of NAC group significantly decreased from 21.0(8.2) to 11.3(5.7) during this study. However, no statistically significant decrease of YBOCS was found in the placebo group. The Cohen's d effect size was 0.83. The mean change of score of resistance/control to obsessions in the NAC and placebo groups was 1.8(2.3) and 0.8(2.1), respectively (P = 0.2). However, the mean score of change for resistance/control to compulsion in the NAC and placebo groups was 2.3(1.8) and 0.9(2.3), respectively. Cohen's d effect size was 0.42. The score of three domains of quality of life significantly decreased in N-Acetylcysteine group during this trial. However, no statistically significant decrease was detected in the placebo group. No serious adverse effect was found in the two groups. Conclusion: This trial suggests that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents. In addition, it is well tolerated.