Background: Children with ADHD and sleep problems have more caregiver deficits and decreased school attendance than children with ADHD but without a sleep problem. We conducted an N-of-1 trial of melatonin for children with ADHD on stimulants. As a follow-up study, we aim to conduct a cost effectiveness analysis (CEA) of melatonin therapy by comparing costs of this condition (of using melatonin) to costs of the baseline condition (usual care with no N-of-1 trial). Methods: The CEA will compare participants who remained on melatonin vs those who chose to cease melatonin. Costs will be determined by medication cost to the caregiver(s), school/work absences, other sleep remedy costs, and health service utilization costs, including incidentals like parking. These costs will be determined at baseline, end of 6-week trial, and 6 months post-trial. We will also calculate Quality-Adjusted Life-Years (QALY) based on responses to PedsQL or SF-12v2 for patients and caregiver(s) and assess differences between remaining on melatonin or not; and assess the intermediate-term effectiveness and adverse effects of melatonin at 6 months. Discussion: We hypothesize that shorter sleep-onset-latency will be associated with improved QALYs for patients and caregivers. We also expect that targeting melatonin to positive responders will be cost effective both for individuals and society. Cost per QALY for positive responders to melatonin is useful for doctors when creating treatment plans since melatonin is not an over-the-counter pharmaceutical in Australia. Trial registration number: ACTRN12614000542695.