Hematopoietic stem cell transplantation (HSCT) is an increasingly common treatment for children with a range of hematological disorders. Conditioning with cytotoxic chemotherapy and total body irradiation leaves patients severely immunocompromised. T‐cell reconstitution can take several years due to delayed restoration of thymic output. Understanding T‐cell reconstitution in children is complicated by normal immune system maturation, heterogeneous diagnoses, and sparse uneven sampling due to the long time spans involved. We describe here a mechanistic mathematical model for CD4 T‐cell immune reconstitution following pediatric transplantation. Including relevant biology and using mixed‐effects modeling allowed the factors affecting reconstitution to be identified. Bayesian predictions for the long‐term reconstitution trajectories of individual children were then obtained using early post‐transplant data. The model was developed using data from 288 children; its predictive ability validated on data from a further 75 children, with long‐term reconstitution predicted accurately in 81% of the patients.