Due to the increasing focus on neurodevelopment in children with congenital heart disease (CHD), early predictive markers are crucial for implementing interventions and improving neurodevelopmental outcomes. As postoperative delirium (PD) is known to have a long-term impact on neurocognitive function in adults, studies on the prevalence of and modifiable risk factors for PD offer new perspectives. We conducted a retrospective, single-centre study screening for PD using the Cornell Assessment of Pediatric Delirium (CAPD). We distinguished PD from iatrogenic withdrawal syndrome (IWS) by using the Withdrawal Assessment Tool 1 (WAT-1). A confirmatory, multivariate regression analysis was performed and included various pre-, intra-, and postoperative variables. The screening compliance rate was 95% among the 311 patients. The prevalence of PD was 40.2%, and 46.4% of the patients developed IWS. Infants were at the highest risk for PD (OR 2.9, p = 0.05). Prolonged mechanical ventilation > 100 h (OR 7.4, p = 0.003), infusion therapy with ketamine (OR 3.3, p = 0.009), IWS (mild: OR 7.7, p = < 0.001, severe: OR 17.0, p = < 0.001) and low cardiac output syndrome (LCOS) (OR 3.9, p = 0.02) were significant predictive risk factors for PD. Overall, PD and IWS are highly prevalent in paediatric cardiac intensive care units (pCICUs), especially in infants and children with prolonged ventilation durations who require multiple sedatives. This is one of the most extensive single-centre studies in the pCICU population, and the results revealed that IWS and lactatemia in the context of LCOS are novel predictors of PD.