We tested the hypothesis that controlled reperfusion with leukocyte-depleted blood could improve myocardial protection by reducing the oxidative stress in patients undergoing myocardial revascularization. Thirty-four patients receiving antegrade/retrograde blood cardioplegia were divided into: group A: 11 patients with ejection fractions (EF) less than 35%, treated with leukocyte-depleted controlled blood reperfusion, group B: 11 patients with EF less than 35% in whom no leukocyte depletion was performed, group C: 6 patients with EF more than 45% treated as group A and group D: 6 patients with EF more than 45% without leukocyte depletion. To asses the oxidative stress, we evaluated total, total oxidized (GSSX), and reduced glutathione (GSH) in coronary sinus plasma, immediately before cross-clamping the aorta (T0), and at 0 (T1), 15 (T2) and 30 (T3) min after unclamping it. In groups A and B a significant shift towards oxidation of redox status of glutathione (GSH/GSSX) at T1 vs T0 was observed. Glutathione redox ratio remained low in group B while in group A it returned to the basal value at T2 with a significant difference from group B at T2 and T3. No differences were observed between groups C and D. In conclusion, our data show that leukocyte-depleted reperfusion can afford a better myocardial protection in patients with left ventricular dysfunction, while it seems unnecessary in patients with normal EF.