The aim of this clinical trial was to evaluate the pulsatile perfusion mode in pediatric patients who had complex cardiac pathologies according to Jenkins stratifications (category 4) undergoing cardiopulmonary bypass procedures (CPB). Patients with transposition of great arteries (TGA) and ventricular septal defect (VSD) were included in this clinical study. Eighty-nine consecutive pediatric patients undergoing open heart surgery for repair of TGA-VSD were prospectively entered into the study and were randomly assigned to either the pulsatile perfusion group (Group P, n = 58) or the nonpulsatile perfusion group (Group NP, n = 31). There were no differences between groups in terms of demographical and intraoperative parameters. The pulsatile group needed significantly less inotropic support (P < 0.05) and had lower lactate levels (P < 0.001), higher urine output (P < 0.01), and higher albumin levels (P < 0.05). In addition, the pulsatile group had less ICU (P < 0.01) and hospital stays (P < 0.001). We conclude that the use of pulsatile flow is a better option and should be considered for repair of the complex congenital heart defects.