Aim: Sirolimus is currently used off-label for pediatric patients with vascular anomalies. However, the optimal dosage regimen for pediatric patients remains controversial. This study aimed to determine the optimal dosing regimen of sirolimus in these patients using a population pharmacokinetic (PK) model. Methods: Prospective study data (7 subjects) were used as the base model without covariates, while the retrospective study data (21 subjects) were used as the base model for external evaluation. The model was assessed using general model-building criteria, and a bootstrap stepwise covariate modeling method was used to identify relevant covariates. Simulations were performed for various scenarios to determine the optimal dosing regimen for maintaining sirolimus trough concentrations within a specific range. NONMEM software (version 7.5) with the first-order conditional estimation method with interaction was used. Results: The final sirolimus model was developed using a 2-compartment model, which was implemented by a maturation function using postmenstrual age (PMA), allometrically scaled body weight to account for size differences, and hemoglobin as a covariate on clearance. Simulations were conducted to propose an optimal dosing regimen. A once-daily dose of 0.01 – 0.1 mg/kg over one month maintained the trough concentration within the range of 5~15 ng/mL, taking into account patient-specific weight and the influence of hemoglobin constrained on PMA. The optimal dose varied by group, within the range of 0.05–0.09 mg/kg. Conclusions: We developed a robust and reliable PK model of sirolimus for pediatric patients with vascular anomalies. Pediatric optimal dosing regimens should be based on individual growth patients.