BACKGROUND To evaluate the safety and effectiveness of tepid perfusion and isothermic blood cardioplegia in coronary surgery. METHODS We studied 200 patients undergoing myocardial revascularization: 100 procedures were performed with moderate systemic hypothermia (28 degrees C) and cold crystalloid cardioplegia (4 degrees C); the other 100 patients received tepid systemic perfusion (TP) (34 degrees C) and intermittent blood cardioplegia at the same temperature according to the minicardioplegia technique (Group 2). The two groups were comparable with regards to age, extent of disease, preoperative left ventricular function and extra-corporeal circulation (ECC) time. RESULTS In the tepid group we observed a higher incidence of spontaneous resumption of cardiac rhythm at cross-clamp removal compared to the hypothermic group (93% vs 34%; p<0.001). No difference was found in cardiac index at specified intervals, myocardial enzymes, inotrope requirements, arrhythmias, need for vasopressors and postoperative blood loss. Fluid balance at the end of ECC was significantly lower in the tepid group (343+/-635 ml vs 883+/-925 ml; p<0.001). Hospital mortality and morbidity were the same in the two groups. CONCLUSIONS Our data suggest that TP and isothermic blood cardioplegia represent a simple, safe and effective method of systemic and myocardial protection which may be an alternative to traditional hypothermia.