Objective To investigate the effect of high-dose creatine phosphate (CP) on myocardial ischemia-reperfusion (I/R) injury in patients undergoing cardiac valve replacement. Methods Two hundred and forty-six ASA Ⅱ or Ⅲ patients aged 42-71 yr weighing 45-80 kg undergoing mitral-aortic valve replacement were randomly assigned into 2 groups: control group ( n = 122) and CP group ( n = 124). CP 10 g in 100 ml normal saline (NS) was infused over 60 min starting from the beginning of operation in group CP. In control group NS 100 ml was infused instead of CP. Blood samples were collected before anesthesia and on 1st and 5th postoperative day for determination of serum CK, CK-MB and LDH activity and cTnI concentration. The number of patients receiving dopamine and adrenaline at the time of return of spontaneous heart beat and 12, 24 and 48 h after operation was recorded. The incidence of arrhythmia (auricular fibrillation, ventricular arrhythmia), myocardial infarct and left ventricular ejection fraction (LVEF) were also compared between the 2 groups. Results Serum CK, CK-MB and LDH activity and cTnI concentration on 1st and 5th postoperative day, the doses of dopamine and adrenalin, the incidence of arrhythmia and myocardial infarct were significantly lower in group CP than in control group. The postoperative LVEF and the incidence of spontaneous recovery of spontaneous heart-beat were significantly higher in group CP than in control group. Conclusion Pretreatment with high dose CP can protect myocardium against I/R injury in patients undergoing cardiac valve replacement under CPB. Key words: Phosphocreatine; Heart valve prosthesis; Myocardial reperfusion injury