The head-up tilt test (HUTT) is a fundamental tool for the clinical diagnosis of unexplained syncope. While HUTT has been extensively employed in adult populations for over three decades, its application in pediatric cases remains relatively limited. A comprehensive literature review was conducted to perform a multi-dimensional evaluation of HUTT in pediatric patients. This review focused on the differences in methodologies and diagnostic criteria for children versus adults, described diagnostic accuracy and safety of HUTT, and summarized risk factors of syncope events during the HUTT. Notable differences in HUTT between children and adults are evident across various parameters such as tilt angle, tilt duration, and the administration of pharmacological agents. In pediatric patients, HUTT not only helps in determining the subtype of orthostatic intolerance but also facilitates the identification of the etiology of unexplained symptoms such as syncope, sighing, palpitations, chest pain, and abdominal pain. Severe adverse events are uncommon
nevertheless, registered events include different types of arrhythmias or even cardiac arrest, temporary aphasia, convulsions, seizure-like activities, and psychological and psychiatric symptoms. Furthermore, the occurrence of syncope events during the HUTT is influenced by multiple factors including age, sex, height, weight, systolic blood pressure, diastolic blood pressure, hemodynamic type, average hemoglobin concentration levels of creatine kinase activity levels genetic predispositions, multivitamin status among others.