BACKGROUND: Although Onyx is widely used to embolize vascular lesions in adults, the safety and efficacy of this liquid embolic agent for use in children are not well studied. OBJECTIVE: To report our experience using Onyx in pediatric patients for a variety of cranial and spinal vascular lesions and tumors to determine its procedural complication rates, types, and clinical consequences and to highlight the indications for and principles of Onyx embolization in pediatric patients. METHODS: All pediatric Onyx embolization cases performed consecutively by the neuroendovascular services at our 2 institutions over a 5-year period were collected retrospectively and analyzed. RESULTS: Over the study period, 105 Onyx embolization procedures were performed in 69 pediatric patients with a mean follow-up of 112 days. Fifty-two patients harbored "primary" vascular lesions (malformations, fistulas, etc), whereas 17 patients had tumors. Complications occurred in 25 of 105 procedures (23.8%) and included ischemic infarct (7), asymptomatic nontarget embolization (4), intracerebral hemorrhage (3), microcatheter-related vessel perforation (3), retained microcatheter (2), cerebral edema (2), dimethyl sulfoxide-induced pulmonary edema (2), facial ischemia (1), and contrast-induced bronchospasm (1). Neurological morbidity occurred transiently after 10 procedures (9.5%) and permanently after 2 procedures (1.9%). There were no procedure-related deaths. Statistical analysis revealed no predictors of complications among the multiple potential risk factors evaluated. CONCLUSION: Our experience suggests that Onyx can be used effectively for embolization of pediatric cranial and spinal vascular lesions and tumors with low permanent morbidity; however, attention must be paid to the technical nuances of and indications for its use to avoid potential complications.