Erythropoietin (EPO) exerts a tissue-protective activity in several non-haematopoietic tissues such as heart, brain, spinal cord and muscle. We evaluated the relationship between pre-operative endogenous EPO blood levels and myocardial damage in patients undergoing cardiopulmonary bypass (CPB). Furthermore, we investigated whether pre-operative administration of a single bolus of 40,000 IU epoetin alpha (EPOalpha) would reduce troponin I or creatine kinase isoenzyme (CK-MB) after on-pump coronary artery bypass graft (CABG) surgery. Sixty-seven patients (45 CABG, 22 valvular surgery) were enrolled. EPO was measured in the pre-surgical period and correlated to post-surgical troponin I and CK-MB peaks. Subsequently, forty patients scheduled for CABG were randomized into two groups, receiving, respectively, a) standard medical and surgical treatment (20 patients) and b) the same treatment plus 40,000 IU of EPOalpha in a single bolus injection in the immediate pre-surgical period (20 patients). In our population, we did not find any correlation between pre-surgical EPO and post-surgical troponin I or CK-MB peaks (p Pearson > 0.05). Furthermore, patients treated with EPOalpha did not show differences compared to the control group in either troponin I (1.7+/-1.8 vs 2.6+/-3.4, p>0.05) or CK-MB (19.6 +/-13.2 vs 17.1+/-12.6, p>0.05) peaks measured in the post-surgical period.