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Objective: Patients with acute coronary syndrome (ACS) undergoing urgent on-pump coronary artery bypass grafting (CABG) are at increased risk for myocardial ischemia/reperfusion injury, but the optimal cardioplegic strategy remains uncertain. This study compared the cardioprotective effects of intermittent warm (IWC) versus cold blood cardioplegia (ICC) in this high-risk cohort. Methods: All patients with acute coronary syndrome (ACS) and urgent indication for on-pump coronary artery bypass grafting (CABG) were prospectively enrolled into the study. Applied cardioplegic strategy (ICC/IWC) was left at the discretion of the surgeon. Groups were compared with regard to the release of markers for myocardial injury (CK-MB, cTnT) and clinical outcomes, including in-hospital mortality and major adverse cardiac events (MACE). Results: From April to September 2010 a total of 65 patients with ACS underwent urgent CABG in our institution. Mean patients age was 67.6±9.8 years. IWC was used in 20 patients (30.8%) while ICC was applied in 45 patients (69.2%). Demographics, intraoperative data (CPB time, cross-clamp time, number of grafts) did not differ between groups. Pre- and postoperative levels of myocardial injury markers (CK-MB, cTnT) were similar in both groups (p=ns). Overall in-hospital mortality was 12.3% (8/65) with a MACE rate of 21.5% (14/65) without intergroup differences. Conclusion: Urgent CABG for ACS is associated to an increased postoperative mortality and morbidity. Our preliminary analysis in this small patients cohort fails to reveal relevant benefits of either cold or warm blood cardioplegia for myocardial protection in this high-risk patients cohort.