Aim To compare the myocardial effects of cardioplegia by warm blood, tepid blood, and cold crystalloid during coronary artery bypass grafting (CABG). Methods Patients undergoing CABG surgery at Kaunas University Hospital between 2000 and 2004 were randomized into three groups (n=156), receiving a different method of cardioplegia. Intermittent antegrade warm blood cardioplegia was used in 51 patients, tepid blood cardioplegia in 50 patients, and cold crystalloid cardioplegia in 55 patients. Mitochondrial function, myocardial ultrastructure, troponin T, and hemodynamic and clinical data were analyzed after surgery. Results All cardioplegic methods similarly affected structural and functional properties of mitochondria and coupling of oxidative phosphorylation, and all lowered the capacity of mitochondria to synthesize ATP. Ultrastructure of myocytes showed slight to moderate injury in the cold crystalloid cardioplegia group. The concentration of troponin T was significantly lower in the warm blood cardioplegia group than in the tepid blood cardioplegia and cold crystalloid cardioplegia groups at 12 hours (0.8 +/- 0.1 ng/mL, 1.9 +/- 0.2 ng/mL, and 2.8 +/- 0.3 ng/mL, respectively; P < 0.001) and 24 hours after surgery (1.0 +/- 0.1 ng/mL, 2.2 +/- 03 ng/mL, and 2.5 +/- 0.3 ng/mL, respectively; P<0.001). Echocardiographic examination after surgery revealed that the changes in the left ventricle diastolic function were similar in all groups, and that systolic function did not change. The warm blood cardioplegia group showed shorter duration of intubation and hospitalization. There were no differences in the need of catecholamine administration, incidence of complications, and duration of stay in the intensive care unit. Conclusions Intermittent antegrade warm blood cardioplegia provides better myocardial protection during CABG surgery, as assessed by the lower release of troponin T, lower fluid balance, shorter duration of tracheal intubation and hospital stay.