Objective: By maintaining native coronary blood flow in on-pump beating heart surgery (OnP-BH) and comparing with OPCAB strategy pump-related effects on myocardial injury and cardiac dysfunction could be specifically differentiated from ischemia/reperfusion-related consequences of surgical coronary revascularization. Methods: In a randomized-prospective design, 40 elective patients with normal EF and three vessels coronary artery disease (left main disease excluded) were assigned to OPCAB or OnP-BH surgery. Before coronary occlusion and 1, 30, 60, and 90min after reperfusion with the LIMA graft, coronary sinus (CS) blood was sampled to determine intraoperative myocardial ischemia (pH, lactate, pO 2 ) and oxidative stress (malondialdehyde, MDA). Additionally to CS blood arterial blood was analyzed 4, 12, and 24h postoperatively to determine myocardial necrosis (CK-MB, cardiac troponin I), myocardial dysfunction (NT-proBNP) and inflammation (C-reactive protein). Results: Groups were identical with regards to age and gender (OPCAB 63.0±6.0 versus OnP-BH 65.3±3.9 y, 20% female patients). Number of grafts were 3.0±0.5 in OPCAB versus 2.9±0.3 in OnP-BH (n.s.) with 44 versus 34% bilateral IMAs and 56 versus 50% complete arterial revascularization. Regarding ischemia, intraoperatively only lactate values increased significantly in the OnP-BH group. Significantly higher CK-MB and troponin I levels were found from LIMA-LAD flow release onwards to 4h postoperatively in the OnP-BH group. NT-proBNP levels were significantly higher in the OnP-BH group during the entire study period. CRP levels were higher in the OnP-BH group 12 and 24h postoperatively. Conclusions: In this randomized study on routine coronary patients with normal ventricular function, OPCAB revealed less myocardial injury than OnP-BH. These findings implicate that CPB slightly affects the myocardium.