Incomplete drainage of blood from around the heart and lungs can lead to retained blood syndrome (RBS) after cardiac surgery. The aim of this study was to assess the incidence of and the outcome after procedures for RBS in patients undergoing isolated coronary artery bypass grafting (CABG). A total of 2764 consecutive patients who underwent isolated CABG from 2006 to 2013 were investigated retrospectively. Patients undergoing any procedure for RBS were compared with patients who did not undergo any procedure for RBS. Multivariate analyses were performed to assess the impact of procedures for RBS on the early outcome. A total of 254 patients (9.2%) required at least one procedure for RBS. Multivariate analysis showed that RBS requiring a procedure for blood removal was associated with significantly increased 30-day mortality [8.3% vs 2.7%, odds ratio (OR) 2.11, 95% confidence interval (95% CI) 1.15-3.86] rates. Procedures for RBS were independent predictors of the need for postoperative antibiotics (51.6% vs 32.1%, OR 2.08, 95% CI 1.58-2.74), deep sternal wound infection/mediastinitis (6.7% vs 2.2%, OR 3.12, 95% CI 1.72-5.66), Kidney Disease: Improving Global Outcomes acute kidney injury (32.7% vs 15.3%, OR 2.50, 95% CI 1.81-3.46), length of stay in the intensive care unit (mean 8.3 vs 2.0 days, beta 1.74, 95% CI 1.45-2.04) and composite major adverse events (21.3% vs 6.9%, OR 3.24, 95% CI 2.24-4.64). These findings were also confirmed in a subgroup of patients with no pre- or postoperative unstable haemodynamic conditions. RBS requiring any procedure for blood removal from pericardial and pleural spaces is associated with an increased risk of severe complications after isolated CABG.