AimsThe occurrence of hyperbilirubinaemia after heart surgery using cardiopulmonary bypass or post‐operative heart failure is fairly common. We investigated the incidence, predictive value, and post‐operative outcome of hyperbilirubinaemia after cardiac surgery in an effort to identify potential risk factors and significance on clinical outcome.Methods and resultsBetween 2006 and 2016, 1272 (10.1%) out of 12 556 patients developed hyperbilirubinaemia, defined as bilirubin concentration >3 mg/dL, during post‐operative course at our institution. All patients who were operated using cardiopulmonary bypass were included. Hepatic dysfunction was diagnosed preoperatively in 200 patients (15.7%), whereas mean model of end‐stage liver disease score was 11.22 ± 4.99. Early mortality was 17.4% with age [hazard ratio (HR) 1.019, 95% confidence interval (CI) 1.008–1.029; P = 0.001], diabetes (HR 1.115, CI 1.020–1.220; P = 0.017), and emergent procedures (HR 1.315, CI 1.012–1.710) as multivariate predictors. Post‐operative predictors were low‐output syndrome (HR 3.193, 95% CI 2.495–4.086; P < 0.001), blood transfusion (HR 1.0, CI 1.0–1.0; P < 0.001), and time to peak bilirubin (HR 1.1, CI 1.0–1.1; P < 0.001). We found an increased correlation with mortality at 3.5 post‐operative day as well as an optimal cut‐off value for bilirubin of 5.35 mg/dL. A maximum bilirubin of 25.5 mg/dL was associated with 99% mortality. Survival analysis showed significantly decreased survival for patients who developed late, rather than early, hyperbilirubinaemia.ConclusionsPost‐operative hyperbilirubinaemia is a prevalent threat after cardiopulmonary bypass, associated with high early mortality. The timing and amount of peak bilirubin concentration are linked to the underlying pathology and are predictors of post‐operative outcome. Patients with late development of steep hyperbilirubinaemia warrant meticulous post‐operative care optimizing cardiac and end organ functions before reaching the point of no return.