• Background: Myocardial protection refers to strategies and techniques used during operation to prevent Ischemic reperfusion injury. These strategies are achieved by cardioplegic solution which can be classified into two main groups. One is based on extracellular components with high potassium, magnesium and bicarbonate levels as cold blood cardioplegia while the other group is based on the intracellular level of electrolytes as (HTK) or (Custodiol). The aim of this study: was to compare the results of Custodiol and cold blood cardioplegia for myocardial protection in double valve replacement. Methodology: This study conducted on (60) patients with double valve replacement receiving Custodiol and Cold Blood Cardioplegia in Benha University Hospital. Results: Custodiol is convenient, simple, safe and more effective than repetitive cold blood cardioplegia in myocardial protection especially postoperative ventilation, complications, inotropic supports, ICU stay and hospital stay periods. Conclusion: This study supports the use of single dose cardioplegia strategy (Custodiol) over Cold Blood Cardioplegia for myocardial protection in complex cardiac surgery.