Background: The use of Custodiol cardioplegia solution may be tempting in cases undergoing long open-heart surgical procedures, given its single dose administration, which offers myocardial protection for a long period. Objective: The aim of the current study is to report our initial experience with the use of Custodial cardioplegia in patients undergoing triple valve surgery, and comparing it with our routinely used cold blood cardioplegia. Patients and Methods: A retrospective observational study including 79 consecutive patients who underwent first-time triple valve surgery in the period between April 2018 and May 2020. Patients were divided into two groups. Group (A) included 31 patients where Custodiol cardioplegia was used, and Group (B) included 48 patients where cold blood cardioplegia was used. The primary endpoint was in-hospital mortality. Secondary endpoints included postoperative levels of CK-Mb, the need for inotropes and the incidence of ventricular fibrillation on aortic declamping. Results: Apart from a higher incidence of ventricular fibrillation on aortic declamping, there was no statistically significant difference between groups in any of the endpoints examined. Conclusion: Custodiol cardioplegia is a safe option for myocardial protection in patients undergoing triple valve surgery. The added cost and the concerns about its efficacy in patients with impaired ventricular function reported by other authors should be borne in mind while considering its use.