Objective To investigate whether the supplement of creatine phosphate sodium with tranexamic acid to cardioplegic solutions improves myocardial protection and blood conservation in off-pump coronary artery bypass graft(OPCABG). Methods 280 patients undergoing OPCABG were randomly assigned to experimental group(n=70), creatine phosphate sodium group(group CP, n=70), tranexamic acid group（group TA, n=70） and control group(n=70). Before CBP they were intravenously given creatine phosphate sodium(100mg/kg) combined with tranexamic acid(30mg/kg), creatine phosphate sodium(100mg/kg), tranexamic acid(30mg/kg), and normal saline respectively. Venous blood was collected preoperatively, and at 0h, 6h, 12h, 24h, 48h, 72h, 7d postoperatively to analyze creatine kinase isoenzyme (CK-MB), troponin (cTnI ) , simultaneously the amount of cumulative chest fluid drainase and inotropic agent and blood transfuison were recorded. Result The plasma concentrations of CK-MB and cTnI in experimental group at 6h, 12h, 24h, 48h, 72h postoperatively were significantly lower than those of group CP , group TA and control group(p<0.05) . The amount of postoperative cumulative chest fluid drainase and blood transfuison in experimental group were also significantly lower than those of other groups(p<0.05). Conclusion For the patients undergoing OPCABG, creatine phosphate sodium combined with tranexamic acid plays an important role in myocardial protection and blood conservation without increasing the surgical mortality and the incidence of postoperative complications.