Objective: To compare efficacy of Omega-3/6 fatty acids (Equazen eye q™) with methylphenidate (MPH) and combined MPH + Omega-3/6 in children with ADHD. Method: Participants (N = 90) were randomized to Omega-3/6, long-acting MPH, or combination for 12 months. ADHD symptoms were assessed using the ADHD Rating Scale and Clinical Global Impressions–Severity (CGI-S) scale. Results: ADHD symptoms decreased in all treatment arms. Although significant differences favoring Omega + MPH over Omega-3/6 alone were found for ADHD Total and Hyperactivity-Impulsivity subscales, results on the Inattention subscale were similar. CGI-S scores decreased slowly and consistently with Omega-3/6, compared with a rapid decrease and subsequent slight increase in the MPH-containing arms. Adverse events were numerically less frequent with Omega-3/6 or MPH + Omega-3/6 than MPH alone. Conclusion: The tested combination of Omega-3/6 fatty acids had similar effects to MPH, whereas the MPH + Omega combination appeared to have some tolerability benefits over MPH.