Background: An abnormality in long chain-polyunsaturated fatty acid (LC-PUFA) levels has been implicated in attention-deficit/ hyperactivity disorder (ADHD). Studies evaluating LC-PUFA supplementation for therapeutic efficacy in ADHD have shown mixed and, therefore, inconclusive results. Methods: Seventy-six male adolescents (age 12-16 years, mean = 13.7) with ADHD were assessed for the effects of 12 weeks omega-3 and omega-6 supplements on biochemical and psychological outcomes in a randomized, placebo-controlled, clinical trial. The primary outcome measure was change in the Conners' Teacher Rating Scales (CTRS) following 12 weeks of supplementation of LC-PUFA or placebo. At baseline, the placebo and treatment groups had comparable levels of LC-PUFA as measured by red blood cell phosphatidylcholine. In the treatment group, supplementation enhanced eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total omega-3 fatty acid levels. Results: No superiority of LC-PUFAs to placebo was observed on the primary outcome. Further, there were no reliable treatment effects on aggression, impulsivity, depression, and anxiety. Conclusions: Future studies should use larger sample sizes and longer supplementation period to detect small-modest effects for clinical recommendations in ADHD.