ABSTRACT Background: Cardiopulmonary bypass (CPB) during open-heart surgery is associated with increased body fluids as a consequence of hemodilution due to the use of CPB. Ultrafiltration (UF) is a method used to decrease the body fluid volume on CPB. Aims and Objectives: This study aimed to compare the effects of combined conventional UF (CUF) and modified UF (MUF) versus MUF on the clinical outcomes of pediatric patients undergoing open-heart surgery for congenital heart disease. Materials and Methods: This was a prospective, single-center, randomized, and double-blinded clinical study that involved 74 pediatric patients undergoing open-heart surgery on CPB. Patient management was standardized. Preoperative Aristotle comprehensive complexity level, ultrafiltrate volumes, hematocrit, hemodynamic data, transesophageal echocardiographically (TEE) determined ejection fraction (EF), fractional area change (FAC), temperature drift, arterial oxygenation, time of extubation, ventilation, comparison of inotropic drugs, postoperative chest tube drainage, cardiac care unit (CCU), and hospital length of stay (LOS) were recorded in both groups. The analysis was conducted using SPSS-23.0, IBM, Armonk, NY, USA. Results: There was no mortality in both groups. Technical difficulties prevented the completion of MUF in two patients out of 37 in the CUF + MUF group. In this study, there were 43.26% of females and 56.75% of males, with a median age of 439 days, a mean weight of 9.98 kg, and an Aristotle Comprehensive Complexity score of level 2. Group CUF + MUF had a greater ultrafiltrate volume of 122 ± 39.7 ml (P = 0.036). The duration of ventilatory support was 11.2 ± 6.4 h versus 34.4 ± 5.7 h (P = 0.013), average CCU LOS was 4.3 ± 3.5 days versus 7.2 ± 3.6 days (P = 0.008), and chest tube drain in the first 48 h was 89.76 ± 34.82 ml versus 106.65 ± 47.29 ml (P = 0.029) in groups CUF + MUF and MUF, respectively. Inotropic infusion requirements were significantly lower in the CUF + MUF group compared to the MUF group. EF and FAC were 14% and 5% higher at 45 min in group CUF + MUF, respectively. Conclusions: The advantage of combining CUF and MUF over MUF is the significant improvement in the hemodynamic status of patients, which significantly decreases the duration of mechanical ventilation, average CCU LOS, inotrope requirements after surgery, and chest tube drain in the first 48 h.