Background. There are few studies describing acetaminophen (APAP) cerebrospinal fluid (CSF) concentrations in children. This current study was undertaken in childrenfrom neonates to adolescentsin order to investigate age-related changes in the plasma to CSF equilibration half-time (Teq) of APAP. Methods. Children (n=41) 1week to 18years of age undergoing (semi) elective surgery for placement or revision of a ventriculo-peritoneal shunt or insertion of a temporary external ventricular drain received a loading dose of 3040mg/kg APAP 1h before scheduled surgery. Blood and CSF samples for APAP concentration analysis were collected during surgery. In those children with a temporary external drain, blood and CSF sampling were extended into the postoperative period. APAP and CSF pharmacokinetics were estimated using non-linear mixed-effects models. Size was standardized to a 70-kg person using allometric 1/4 power models. Results. Median (2575th percentile) age and weight of the patients included in this study were 12months (362months) and 10.0kg (5.820.0kg). Median (2575th percentile) time between APAP loading dose administration and collection of blood samples and median time (2575th percentile) between APAP loading dose and collection of CSF were, respectively, 125min (95210min) and 133min (33202min). The population mean Teq, standardized to a 70-kg person, was 1.93h (CV 43%), an estimate similar to that described in adults (2.1h). There was no relationship between age and Teq other than that predicted by size. APAP plasma concentrations ranged from 0.0mg/l to 33.0mg/l, APAP CSF concentrations ranged from 0.0mg/l to 21.0mg/l. Conclusion. Size rather than bloodbrain-barrier maturation determines Teq changes with age in children. We predict a neonate (3.5kg), 1-year-old child (10kg), 5-year-old child (20kg), 10-year-old child (30kg) and adult (70kg) to have Teq values of 0.9, 1, 1.4, 1.6, and 1.93h, respectively.