The objective of this study was to test whether a previous observed Acetyl-L-carnitine (ALC) treatment effect could be repeated in an ALC adjunctive therapy treatment trial of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This was a six-week, randomized clinical trial undertaken in an outpatient child and adolescent clinic. Subjects included 40 outpatients (28 boys and 12 girls) between the ages of 7-13 who met the DSM-IV-TR diagnostic criteria for ADHD. All study subjects were randomly assigned to receive treatment using capsules of ALC doses ranging from 500 to 1,500 mg/day depending on the weight of the child plus methylphenidate at a dose of 20-30 mg/day depending on weight or Placebo plus methylphenidate at a dose of 20-30 mg/day depending on weight. The principal measure of outcome was the Teacher and Parent attention deficit/hyperactivity disorder Rating Scale- IV. No difference was observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 0.10; P = 0.74 and df = 1; F = 0.22; P = 0.63 respectively). Side effects consisting of headache and irritability were observed more frequently in the methylphenidate plus placebo group. The results of this study do not support the application of ALC as an adjunctive therapy to methylphenidate in children and adolescents with ADHD.