AIM: This study aimed to compare the efficacy of the routinely used modified del Nido cardioplegia and Plegisol® solution in myocardial protection. METHODS: In this retrospective study, patients who underwent cardiopulmonary bypass (CPB) guided cardiac surgery and received del Nido cardioplegia solution (Group 1) and Plegisol® solution (Group 2) were compared in terms of early clinical data and myocardial protection. RESULTS: This study included 68 patients with similar demographic characteristics who received 38 modified del Nido cardioplegia and 30 Plegisol® solutions. Creatine kinase-myocardial bound (CK-MB) and cardiac troponin T (CTnT) levels on postoperative day 1 and CTnT levels on postoperative day 5 were higher in Group 2 and there was a significant difference between the groups (p = 0.025, p = 0.001, p = 0.001, respectively). In addition, the postoperative inotrope requirement and postoperative vasoactive-inotropic score were higher in Group 2 and there was a significant difference between the two groups (p = 0.004, p = 0.002, respectively). CONCLUSIONS: In this study, the del Nido cardioplegia solution was found to be more advantageous regarding the need for intracardiac defibrillation and myocardial necrosis, although it showed similar results in some points when compared with the Plegisol® solution.