BACKGROUND We performed a prospective randomized trial to compare intermittent antegrade warm blood cardioplegia with intermittent antegrade and retrograde cold crystalloid cardioplegia. METHODS Two hundred consecutive patients scheduled for isolated coronary bypass surgical procedures were randomized into two groups: Group 1 (n = 92) received cold crystalloid cardioplegia with moderate systemic hypothermia, group 2 (n = 108) received intermittent antegrade warm blood cardioplegia with systemic normothermia. Preoperative, intraoperative, and postoperative data were prospectively collected. RESULTS For the same median number of distal anastomoses, cardiopulmonary bypass duration and total ischemic arrest duration (57.3 +/- 20.5 versus 75 +/- 22.1 minutes, p < 0.001) were shorter in group 2 than in group 1. Apart from a higher right atrial pressure in the cold cardioplegia group, no hemodynamic difference was observed. Aspartate aminotransferase, creatine kinase-MB fraction, and cardiac troponin I levels were significantly lower in group 2 than in group 1. Outcome variables were not significantly different. CONCLUSIONS Intermittent antegrade warm blood cardioplegia results in less myocardial cell damage than cold crystalloid cardioplegia, as assessed by the release of cardiac-specific markers. This beneficial effect has only marginal clinical consequences. Normothermic bypass has no deleterious effect on end-organ function.