Background Delirium is acute brain dysfunction associated with serious illness. Emerging data indicate that delirium occurs in greater than 20% of children in pediatric intensive care units. Cardiac bypass surgery is a known risk factor for delirium in adults, but has never been systematically studied in pediatrics. Objectives To describe the incidence of delirium in pediatric patients after cardiac bypass surgery, and explore associated risk factors and effect of delirium on in-hospital outcomes. Design Prospective observational single-center study. Setting Fourteen-bed pediatric cardiothoracic intensive care unit (PCICU). Patients One hundred and ninety four consecutive admissions following cardiac bypass surgery, age one day to 21 years. Interventions Subjects were screened for delirium daily using the Cornell Assessment of Pediatric Delirium. Measurements and Main Results Incidence of delirium in this sample was 49%. Delirium most often lasted 1–2 days, and developed within the first 1–3 days after surgery. Age less than two years, developmental delay, higher RACHS-1 score, cyanotic disease, and albumin less than three were all independently associated with development of delirium in a multivariable model (all p values <0.03). Delirium was an independent predictor of prolonged ICU LOS, with patients who were ever delirious having a 60% increase in ICU days compared to patients who were never delirious (p<0.01). Conclusions In our institution, delirium is a frequent problem in children after cardiac bypass surgery, with identifiable risk factors. Our study suggests that cardiac bypass surgery significantly increases children’s susceptibility to delirium. This highlights the need for heightened, targeted delirium screening in all PCICUs to potentially improve outcomes in this vulnerable patient population.