RATIONALE and OBJECTIVE Delirium assessments in critically ill infants and young children pose unique challenges due to evolution of cognitive and language skills. The objectives of this study were to determine the validity and reliability of a fundamentally objective and developmentally appropriate delirium assessment tool for critically ill infants and preschool-aged children, and to determine delirium prevalence. DESIGN and SETTING Prospective, observational cohort validation study of the PreSchool Confusion Assessment Method for the ICU (psCAM-ICU) in a tertiary medical center pediatric ICU. PATIENTS Participants aged 6 months to 5 years and admitted to the pediatric ICU regardless of admission diagnosis were enrolled. INTERVENTIONS, MEASUREMENTS and MAIN RESULTS An interdisciplinary team created the psCAM-ICU for pediatric delirium monitoring. To assess validity, patients were independently assessed for delirium daily by the research team using the psCAM-ICU and by a child psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders criteria. Reliability was assessed using blinded, concurrent psCAM-ICU evaluations by research staff. A total of 530-paired delirium assessments were completed among 300 patients, with a median age of 20 months (IQR 11, 37) and 43% requiring mechanical ventilation. The psCAM-ICU demonstrated a specificity of 91% (95%CI 90, 93), sensitivity of 75% (72, 78), negative predictive value of 86% (84, 88), positive predictive value of 84% (81, 87), and a reliability kappa statistic of 0.79 (0.76, 0.83). Delirium prevalence was 44% using the psCAM-ICU and 47% by the reference-rater. The rates of delirium were 53% vs. 56% in patients < 2 years of age and 33% vs. 35% in patients ≥ 2 - 5 years of age using the psCAM-ICU and reference-rater respectively. The short-form psCAM-ICU maintained a high specificity (87%) and sensitivity (78%) in post-hoc analysis. CONCLUSIONS The psCAM-ICU is a highly valid and reliable delirium instrument for critically ill infants and preschool-aged children, in whom delirium is extremely prevalent.