Context The literature on melatonin as a sedative agent in children is limited. Objective To conduct a systematic review of studies assessing the efficacy and safety of melatonin for non- operating room sedation in children. Methods Medline, Embase, Cochrane Library and Cumulative Index to Nursing and Allied Health were searched until 9 April 2020 for studies using melatonin and reporting one of the prespecified outcomes of this review. Two authors independently assessed the eligibility, risk of bias and extracted the data. Studies with a similar study design, comparator and procedure were pooled using the fixed-effect model. Results 25 studies (clinical trials=3, observational studies=9, descriptive studies=13) were included. Melatonin was used for electroencephalogram (EEG) (n=12), brainstem evoked response audiometry (n=8) and magnetic resonance imaging (MRI) (n=5). No significant differences were noted on meta-analysis of EEG studies comparing melatonin with sleep deprivation (SD) (relative risk (RR) 1.06 (95% CI 0.99 to 1.12)), melatonin with chloral hydrate (RR 0.97 (95% CI 0.89 to 1.05)) and melatonin alone with melatonin and SD combined (RR 1.03 (95% CI 0.97 to 1.10)) for successful procedure completion. However, significantly higher sedation failure was noted in melatonin alone compared with melatonin and SD combined (RR 1.55 (95% CI 1.02 to 2.33)) for EEG. Additionally, meta-analysis showed lower sleep latency for melatonin compared with SD (mean difference −10.21 (95% CI −11.53 to −8.89) for EEG. No major adverse events were reported with melatonin. Conclusion Although several studies were identified, and no serious safety concerns were noted, the evidence was not of high quality to establish melatonin’s efficacy for non-operating room sedation in children.