We retrospectively analyzed early results of coronary artery bypass grafting (CABG) surgery using two different types of cardioplegia for myocardial protection: antegrade intermittent warm blood or cold crystalloid cardioplegia. From January 2015 to October 2016, 330 consecutive patients underwent isolated on-pump CABG. Cardiac arrest was obtained with use of warm blood cardioplegia (WBC group, n = 297) or cold crystalloid cardioplegia (CCC group, n = 33), according to the choice of the surgeon. Euroscore II and preoperative characteristics were similar in both groups, except for the creatinine clearance, slightly lower in WBC group (77.33 ± 27.86 mL/min versus 88.77 ± 51.02 mL/min) (P < 0.05). Complete revascularization was achieved in both groups. In-hospital mortality was 2.0% (n = 6) in WBC group, absent in CCC group. The required mean number of cardioplegia's doses per patient was higher in WBC group (2.3 ± 0.8) versus CCC group (2.0 ± 0.7) (P = 0.045), despite a lower number of distal coronary artery anastomoses (2.7 ± 0.8 versus 3.2 ± 0.9) (P = 0.0001). Cardiopulmonary and aortic cross-clamp times were similar in both groups. The incidence of perioperative myocardial infarction (WBC group 3.4% versus CCC group 3.0%) and low cardiac output syndrome (4.4% versus 3.0%) were similar in both groups. As compared with WBC group, in CCC group CK-MB/CK ratio >10% was lower during each time points of evaluation, with a statistical significant difference at time 0 (4% ± 1.6% versus 5% ± 2.5%) (P = 0.021). In presence of complete revascularization, despite the value of CK-MB/CK ratio >10% was less in the CCC group, clinical results were not affected by both types of cardioplegia adopted to myocardial protection. As compared with cold crystalloid, warm blood cardioplegia requires a shorter interval of administration to achieve better myocardial protection.