OBJECTIVES In cardiac surgery, the association between red blood cell (RBC) transfusion and clinical outcome is elusive. We investigated in a large cohort of patients who underwent isolated coronary artery bypass grafting (CABG) the effect of transfusion of 1–2 units of leucocyte-depleted RBCs on mortality and multiorgan failure. METHODS The investigation included all patients from July 2009 to June 2014 who underwent CABG at our institution and received no (n = 1478) or 1–2 units of RBCs (n = 1528). The primary end-point was 30-day mortality; secondary end-points were major organ dysfunction. A subgroup analysis assessed the effect of the duration of RBC storage on patient outcome. Statistical analysis was performed using propensity score (PS) adjustment. RESULTS The 30-day mortality rate was 0.3% in the RBC− group and 0.2% in the RBC+ group. Compared with the RBC− group, PS-adjusted odds ratio (OR) of 30-day mortality in the RBC+ group was 0.29 95% confidence interval (CI): 0.06–1.50; P = 0.14. PS-adjusted OR of a ‘prolonged intensive care unit (ICU) stay’ (>48 h) was significantly higher in the RBC+ group than in the RBC− group OR 1.49 (95% CI: 1.14–1.95); P = 0.004, but major clinical complications such as low cardiac output syndrome, stroke, haemofiltration, wound infection and prolonged mechanical ventilator support (>24 h) did not differ significantly between groups. Duration of blood storage was not independently associated with clinical outcome. CONCLUSIONS Our data do not indicate a transfusion-related increase in mortality and multiorgan failure in patients undergoing isolated CABG.