Anti-thymocyte globulin (ATG) is used in pediatric allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host-disease (GvHD) and graft failure (GF). Poor or delayed T-cell recovery, associated with increased mortality, is the main toxicity of ATG. Model-based precision dosing of ATG (MBD-ATG) minimizes toxicity while maintaining efficacy. We report updated results of the single-arm phase II PARACHUTE trial investigating MBD-ATG, combined with real-world experience with identical MBD-ATG. Consecutive pediatric patients receiving a first T-cell replete HCT for any indication were evaluated. Results were compared to historical patients receiving conventional fixed ATG dosing (FIX-ATG). Primary outcome was overall survival (OS). The MBD-group consisted of 214 patients (58 trial patients, 156 real-world patients); 100 patients received FIX-ATG. MBD-ATG led to superior OS compared to FIX-ATG (hazard ratio [HR] for death 0.56, 95% confidence interval [CI] 0.34-0.93, p=0.026), mainly due to lower treatment related mortality (TRM; HR 0.51, 95% CI 0.29-0.92, p=0.025). Successful T-cell reconstitution (>0·05 × 10⁹ CD4+ T-cells/L twice within 100±3 days after HCT) was improved in MBD-ATG versus FIX-ATG (87%±2% versus 47%±5%, p<0.0001). The improved T-cell reconstitution led to lower TRM (HR 0.19, 95% CI 0.09-0.36, p<0.0001). Incidence of grade 2-4 acute GvHD was comparable, while chronic GvHD (HR 0.35, 95% CI 0.17-0.72, p=0.004) and GF (HR 0.36, 95% CI 0.13-0.97, p=0.044) were both less frequent in MBD-ATG compared to FIX-ATG. MBD-ATG results in improved OS and reduced TRM, while reducing chronic GvHD and GF. This easy-to-implement approach can improve outcomes after pediatric HCT though confirmatory studies are urgently needed.