Background: Several cardioplegic solutions are available for myocardial preservation. The superiority of intracellular over extracellular cardioplegia is still debated. Our study aimed to compare the results of Custodiol® and blood Cardioplegia for myocardial protection in double valve replacement surgery. Methods: This is a prospective study that included 301 patients. We grouped the patient into; Group A (n= 135) had Custodiol® cardioplegia, and Group B (n= 166) had cold blood cardioplegia. We included patients who had double valve surgery and excluded redo, emergency procedures, and patients who had concomitant coronary artery bypass grafting. Results: Patients in Group A were significantly younger (43 ±9 vs. 47 ±10, P