Objective: Ventricular septal defect (VSD) is the most common pathology among congenital heart diseases. Surgical closure, transcatheter closure or medical follow-up are among the treatment strategies. Surgical closure of VSD can now be safely performed with low morbidity and mortality. In this study, we aimed to compare the efficacy of blood cardioplegia and del Nido cardioplegia during VSD operation. Material and Method: In our Pediatric Cardiovascular Surgery Clinic, we retrospectively evaluated 186 patients, between 6 weeks and 18 years of age, who underwent operation due to isolated VSD between September 2013 and December 2017. Patients were divided into two groups as Group 1 (n = 108 using blood cardioplegia) and Group 2 (n = 78 using del Nido cardioplegia). Pre-operative data, peri-operative data and postoperative data of patients were retrospectively recorded and reviewed in detail. Findings: 153 patients (82.2%) were under 5 years old, 24 (12.9%) were between 5 and 10 years old, and 9 (4.8%) were between 10 and 20 years of age. 112 (60.2%) of the patients were male and 74 (39.8%) were female. The mean age of the patients was 3.8 +/- 2.08 in Group 1 and 4.2 +/- 2.13 in Group 2. There was no statistically significant difference in preoperative demographic data between Group 1 and Group 2 patients (p> 0.05). The duration of cardiopulmonary bypass (CPB), duration of intubation, intensive care unit stay and discharge time were found to be statistically significant when compared with Group 1 (p < 0.05). Result: Congenital heart disease cases can have a long operation time. In the light of our findings, we recommend the use of del Nido cardioplegia, which is administered a single-time and reduces inotropic need and duration of operation as well as significantly reduce extubation and discharge times, instead of blood cardioplegia which is given every twenty minutes. It can be said that del Nido cardioplegia can be safely used in the cases of congenital heart surgery, although it is difficult to give a definitive judgment due to the inadequacy of our case count.