The vancomycin dosing range for safe and effective treatment remains uncertain for children who had corrective surgery for a congenital heart disease (CHD). We aimed to determine the vancomycin dosing requirements for this subgroup of patients.This prospective cohort study included children younger than 14 years old with CHD who received intravenous vancomycin for at least 3 days at the Pediatric Cardiology section of King Abdulaziz Medical City, Riyadh.In total, 140 pediatric patients with CHD were included with a median age of 0.57 years (interquartile range 0.21–2.2). The mean vancomycin total daily dose (TDD), 37.71 ± 6.8 mg/kg/day, was required to achieve a therapeutic trough concentration of 7–20 mg/L. The patient’s age group and the care setting were significant predictors of the vancomycin dosing needs. Neonates required significantly lower doses of 34 ± 6.03 mg/kg/day (P = .002), and young children higher doses of 43.97 ± 9.4 mg/kg/day (P = .003). The dosage requirements were independent of the type of cardiac lesion, cardiopulmonary surgery exposure, sex, and BMI percentile. However, the patients in the pediatric cardiac ward required higher doses of vancomycin 41.08 ± 7.06 mg/kg/day (P = .039). After the treatment, 11 (8.5%) patients had an elevated Scr, and 3 (2.3%) patients developed AKI; however, none of the patients’ sociodemographic factors or clinical variables, or vancomycin therapy characteristics was significantly associated with the renal dysfunction.Overall, the vancomycin TDD requirements are lower in pediatric post-cardiac surgery compared to non-cardiac patients and are modulated by several factors.