Objective: This study compares risk factors, clinical presentation, and outcomes after posterior circulation (PCAIS) and anterior circulation arterial ischemic stroke (ACAIS) in neonates and children. Methods: International multicenter observational study including neonates and children up to 18 years of age with arterial ischemic stroke (AIS), comparing clinical and radiological features according to stroke location. Results: Of 2,768 AIS cases, 507 (18%) were located in the posterior circulation, 1,931 (70%) in the anterior circulation, and 330 (12%) involved both. PCAIS was less frequent in neonates compared to children (8.8% versus 22%, p<0.001). Children with PCAIS were older than children with anterior circulation arterial ischemic stroke (ACAIS), (median age 7.8 (IQR 3.1-14) versus 5.1 (IQR 1.5-12) years, p<0.001), and more often presented with headache (54% versus 32%, p<0.001) and a lower PedNIHSS score (4 (IQR 2-8) versus 8 (IQR 3-13), p=0.001). Cervicocephalic artery dissections (CCAD) were more frequent (20% versus 8.5%, p<0.001), while cardioembolic strokes were less frequent (19% versus 32%, p<0.001) in PCAIS. Case fatality rates were equal in both groups (2.9%). PCAIS survivors had a better outcome (normal neurological examination at hospital discharge in 29% versus 21%, p=0.002) than ACAIS survivors, although this trend was only observed in children and not in neonates. Conclusion: PCAIS is less common than ACAIS in both neonates and children. Children with PCAIS are older, have a higher rate of CCAD, lower clinical stroke severity, and better outcome than children with ACAIS.