STUDY OBJECTIVES: Dravet syndrome is a severe developmental and epileptic encephalopathy, in which 75% of patients have sleep disturbance. Melatonin is often used for sleep problems in childhood; however, there is no quality evidence supporting its use in Dravet syndrome. We hypothesized that melatonin would increase total sleep and quality of life for patients with Dravet syndrome. METHODS: A double-blind crossover randomized placebo-controlled trial was conducted, comparing 6 mg regular-release melatonin to placebo for patients with Dravet syndrome and sleep disturbance. The primary outcome measure was total sleep measured by actigraphy, with secondary outcomes including wakefulness after sleep onset (WASO), Sleep Disturbance Scale in Children and Quality of Life in Children with Epilepsy 55 questionnaires, caregiver reports of clinical change, seizure diary and serum antiepileptic drug levels. We also compared actigraphy data of patients with Dravet syndrome to an age-matched healthy control group. RESULTS: A total of 13 patients completed the study. There was no difference in total sleep or WASO between melatonin and placebo. However, of the 11 patients for whom caregivers reported a clear clinical difference between treatments (blinded), 8 reported improvement on melatonin ( CONCLUSIONS: Melatonin did not increase total sleep; however, blinded caregiver reports indicate treatment with melatonin provided considerable clinical benefit for some patients with Dravet syndrome and sleep disturbance. CLINICAL TRIAL REGISTRATION: Registry: Australian Government Department of Health, Therapeutic Goods Administration under the Clinical Trials Notification Scheme (protocol number 2241).