IntroductionCranio‐spinal radiotherapy (CSI) is used to treat central nervous system malignancies in paediatric, adolescent/young adult (AYA), and adult patients. Its delivery in the paediatric/AYA population is particularly challenging across different age groups. This study aims to assess the setup variations and dosimetric impact of CSI in paediatric and AYA patients.MethodsThis retrospective analysis included, 10 paediatric and AYA patients (aged 4–25) who underwent volumetric modulated arc therapy (VMAT) CSI between 2016 and 2022. Patient characteristics, diagnoses, prescribed CSI doses, and fractionation details were assessed. CT simulation and treatment planning followed standard protocols with setup errors were quantified by comparing daily treatment setup images with the planned position. The study evaluated the dosimetric impact on target volumes and organs at risk (OARs).ResultsThe setup errors were identified, ranging from 0.5 to 6.2 mm in different directions, especially in the cranio‐caudal direction. Despite these variations, there was minimal impact observed on the coverage of clinical target volumes (CTV) and doses to OARs (<1% relative change).ConclusionEnsuring precise setup in paediatric and AYA patients undergoing CSI is essential to maintain adequate CTV coverage. Although occasional substantial setup variations occurred during treatment, they had a limited impact on CTV coverage and OAR doses when infrequent. Appropriate planning target volume (PTV) margins can effectively compensate for occasional shifts. However, systematic errors could compromise treatment quality if undetected. Regular off‐line review of patient set‐up trends is recommended.