The aim of this study was to assess whether the continuous retrograde blood cardioplegia ensures prolonged aortic cross-clamping time without increasing the operative risk. From 1996 to 2003, 204 consecutive patients who had cardiac procedure requiring aortic cross-clamping time > or = 150 min, were prospectively included in this study: low risk group (EuroSCORE < or = 2) 50 patients, medium risk group (EuroSCORE 3-5) 68 patients, high risk group (EuroSCORE > or = 6) 86 patients. The myocardial protection associated induction of cardiac arrest by antegrade injection of hyperkalemic warm blood, continuous retrograde intermediate lukewarm (20 degrees C) blood cardioplegia, retrograde warm blood reperfusion and systemic normothermia. The mean aortic clamping time was 187+/-45 min (range 150-436 min). The mean cardiopulmonary bypass time was 245+/-73 min (range 168-653 min). The operative mortality was 8.3% (17 patients). The mean predicted mortality of the population studied (EuroSCORE logistic method) was 8.4%+/-12 (range 0.87%-76.15%) with a 95% confidence interval of 6.7% to 10%. The observed mortality was not different from the predicted mortality. Continuous retrograde intermediate lukewarm blood cardioplegia associated with systemic normothermia allows prolonged aortic clamping time for complex intervention without increase of operative mortality and morbidity.