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Objective: To compare the efficacy and safety of ketamine alone with those of ketamine‐dexmedetomidine combination for sedation during brain CT in paediatric patients with head injuries. Methods: We retrospectively analysed the data of paediatric patients who underwent sedation for brain CT at the ED. We included patients aged 6 months to 6 years with American Society of Anesthesiologists physical status I or II. The sedative protocol involved the administration of intramuscular (IM) ketamine 3 mg/kg (K), ketamine 2 mg/kg with dexmedetomidine 1.5 μg/kg (KD) or ketamine 1.5 mg/kg with dexmedetomidine 1.5 μg/kg (low‐KD). The primary and secondary outcomes were sedation failure and adverse events, respectively. Results: We included 77 patients; among them, 28, 23 and 26 were in the K, KD and low‐KD groups, respectively. In multivariable analysis, the combination groups (KD and low‐KD groups) were significantly associated with a lower possibility of sedation failure compared to the K group (adjusted odds ratio, 0.12; 95% confidence interval, 0.02–0.56). Moreover, there were no significant differences in adverse events between the groups, and the sedation‐related time variables also did not significantly differ among the three groups. Conclusions: Our findings indicated that a combination of IM ketamine‐dexmedetomidine provides effective sedation for paediatric patients undergoing brain CT without significant adverse events. Further research is needed to investigate the potential benefits of using lower doses of ketamine in combination. [ABSTRACT FROM AUTHOR]