As recently reported in the literature, aerobic cardiac surgery (normothermic total body perfusion + continuous normothermic blood cardioplegia) might achieve optimal heart protection by virtually eliminating myocardial ischemia during aortic cross-clamping. Two-hundred and fifty consecutive patients underwent cardiac surgery by this technique. Mean cross-clamp time was 72.6 +/- 30.7 minutes. Ten patients (4%) died, 20 (8%) needed major inotropic support and 8 (3.2%) required circulatory assistance. Two-hundred and twenty-three patients (89.2%) returned spontaneously to normal sinus rhythm and 8 (3.2%) had evidence of perioperative myocardial infarction. Nineteen patients (7.6%) had a cross-clamp time longer than 120 minutes and no significant difference in mortality was observed with those undergoing a shorter cross-clamping. When comparing 154 patients receiving retrograde continuous normothermic blood cardioplegia induction with 46 receiving antegrade induction, no difference was found in perioperative parameters, mortality and morbidity. By univariate analysis, impaired preoperative LV performance was identified as the only risk factor for operative mortality. In our experience aerobic cardiac surgery appears most suitable for emergency and redo operations, extensive coronary revascularization, complex mitral reconstruction, aortic valve replacement (particularly with unstented biological prostheses), cardiac transplants and whenever two or more valvular and/or coronary procedures are associated. Retrograde induction is as effective as antegrade and simplifies the technique, facilitating unmodified continuous normothermic blood cardioplegia in different anatomical and clinical situations.